Objective: Children and adolescents with a history of traumatic brain injury (TBI) are at increased risk for developing social incompetence and impairment in broad psychosocial functioning. The aim of this study was to examine the relationship between history of TBI, social competence, and broad psychosocial functioning using meta-analytic methods. Methods: Studies relating to social outcome following pediatric TBI were searched for using scientific, academic databases. Sixteen studies (N=2,005) met inclusion criteria, and relevant data relating to social functioning was extracted. Meta-analytic methods were used in order to obtain Hedges's g effect size data for mild, moderate, and severe TBI groups. Meta-regressions were also used to examine the effect of potential moderating variables, including Glasgow Coma Scale (GCS), socioeconomic status (SES), gender, control group (typically developing (TD) or orthopedic injury (OI)), and time/age related variables. Finally, publication bias was calculated using funnel plots and Rosenthal's fail-safe N. Results: A dose-response effect was observed with mild (Hedges's g = -0.387), and moderate (Hedges's g = -0.459) groups demonstrating smaller effects when compared to the severe group (-0.814) on measures of broad psychosocial function. A dose-response effect was also observed on measures of social competence, with mild (Hedges's g = -0.098) and moderate (Hedges's g = -0.450) TBI groups demonstrating smaller effect sizes when compared to the severe TBI group (Hedges's g = -0.832). The GCS was a significant predictor of both broad psychosocial functioning (B = 0.065, p < 0.001) and social competence (B = 0.079, p < 0.001), such that more severe injuries predicted poorer social outcomes. Gender was a significant predictor of effect size (B = 0.018, p = 0.05), such that higher proportions of females was associated with smaller effect sizes. Finally, the type of control group used in these studies was also a significant predictor of effect size (B = 0.369, p = 0.03), such that studies that used TD produced larger effect sizes when compared to studies that used OI. Overall, there was little evidence for publication bias. Conclusions: Children and adolescents with a history of TBI demonstrated significant differences from their peers in social competence and broad psychosocial functioning following TBI. The severity of the injury is important in understanding and predicting social outcomes following pediatric TBI. Implications of these findings are discussed.

Estudamos a relação entre local e tipo da lesão cerebral com a gravidade da disfagia, e a relação entre o grau de comprometimento motor com a gravidade da disfagia em crianças com paralisia cerebral. Foi um estudo retrospectivo de exames de videofluoroscopia da deglutição e ressonância magnética cerebral de crianças com diagnóstico de paralisia cerebral e disfagia, atendidas do Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto (HCFMRP), Universidade de São PauloBrasil, de 2008 a 2016. Foi realizada analise descritiva dos dados e utilizado o teste exato de Fisher para verificar a relação entre as variáveis estudadas. Foram incluídos na pesquisa exames de 20 crianças com idades ao exame de ressonância magnética entre 2 anos e 1 mês de vida a 10 anos e 2 meses, e ao exame de videofluoroscopia da deglutição entre 9 meses a 16 anos e 2 meses. Quanto ao gênero, seis crianças eram do sexo feminino, e 14 do sexo masculino. Com relação à classificação da função motora grossa, duas crianças eram do nível III, cinco do nível IV e 13 do nível V. Quanto a gravidade da disfagia, sete crianças apresentaram disfagia leve/moderada, três com disfagia moderada e 10 crianças com disfagia moderada/grave. As principais alterações evidenciadas na ressonância magnética, quanto à localização da lesão, foram em corpo caloso (60%), ventrículos cerebrais (60%), substancia branca (55%), tronco encefálico (35%) e cerebelo (15%). Os tipos de lesões cerebrais mais freqüentes foram encefalopatia hipóxico-isquêmica (35%), leucomalacia periventricular (25%) e encefalomalacia multicistica (15%). Não houve relação entre o local da lesão cerebral e gravidade da disfagia, entretanto houve relação entre o tipo de lesão cerebral e a gravidade do distúrbio de deglutição (p=0,02). Além disso, houve relação entre a gravidade da disfagia e o grau de comprometimento da função motora grossa. Deste modo, a gravidade da disfagia foi relacionada com encefalomalacia multicística e com o comprometimento da função motora grossa, e nossos resultados mostram a importância da avaliação de deglutição tão logo, nestes pacientes, seja realizado o diagnóstico médico. Além disso, ressaltamos a importância da avaliação da deglutição em todos graus de lesão, devido à presença de disfagia leve a intensa. / We studied the relationship between site and type of brain injury with the severity of dysphagia, and the relationship between the degree of motor impairment and the severity of dysphagia in children with cerebral palsy. It was a retrospective study of videofluoroscopy examinations of swallowing and magnetic resonance imaging of children diagnosed with cerebral palsy and dysphagia, attended at Hospital das Clinicas of the Ribeirão Preto Medical School (HCFMRP), University of São Paulo-Brazil, from 2008 to 2016. A descriptive analysis of the data was performed and Fisher\'s exact test was used to verify the relationship between the variables studied. Included in the study were examinations of 20 children aged between 2 years and 1 month of life to 10 years and 2 months, and videofluoroscopy of swallowing between 9 months and 16 years and 2 months. Six children were female, and 14 were male. Regarding the classification of gross motor function, two children were of level III, five of level IV and 13 of level V. Regarding the severity of dysphagia, seven children presented mild/moderate dysphagia, three with moderate dysphagia and 10 children with moderate/severe dysphagia. The most freqeunt lesions seen in magnetic ressonance imaging (MRI) were in the corpus callosum (60%), cerebral ventricles (60%), white matter (55%), brainstem (35%) and cerebellum (15%). The most frequent types of brain lesions were hypoxicischemic encephalopathy (35%), periventricular leukomalacia (25%) and multicystic encephalomalacia (15%). There was no relationship between the site of the brain lesion and the severity of dysphagia, however, there was a relationship between the type of brain injury and the severity of the swallowing disorder (p = 0.02). In addition, there was a relationship between the severity of dysphagia and the degree of impairment of gross motor function. Thus, the severity of dysphagia was related to multicystic encephalomalacia and the involvement of gross motor function, and our results show the importance of swallowing assessment as soon as the medical diagnosis is made in these patients. In addition, we emphasize the importance of evaluating swallowing in all degrees of injury, due to the presence of mild to severe dysphagia

The incidence of mild blast traumatic brain injuryhas risen due tothe increased use of improvised explosive devices (IEDs) in militaryconflicts. Mild blast TBI (mbTBI) is especially relevant due to its lack of acutely observable symptoms, and to its association with long-term neurodegenerative and neuropsychiatric disorders. Predominantly, TBI patients often suffer from chronic stress, neuropathic pain and headaches, which greatly compromise the health and quality of life of these individuals. Treatments for neuropathic pain have been empirically found and produce little effect in lessening neuropathic pain, likely due to the lack of targeted therapies. This highlights the need for better understanding of the molecular mechanisms underlying neuropathicpain, TBI and chronic stress that could lead to mechanistic therapeutic targets. Oxidative stress is an important mechanism of the pathophysiology of neuropathic pain, TBI and chronic stress. We hypothesize that acrolein, an endogenously formed neurotoxin, is able to stay active in the body for up to 10 days, is involved in the pathophysiology of neuropathic pain in TBI and chronic stress. This study aims to correlate acrolein elevation in the body with neuropathic pain, deepen the understanding of underlying mechanisms of pain in TBI and chronic stress, and mitigate this pain with acrolein scavenging. The ultimate goal of this research is to provide therapies for TBI and chronic stress patients that can eliminate pain and significantly improve their healthand quality of life

Thesis advisor: Belle Liang / Traumatic brain injury (TBI) survivors often experience isolation from their primary support network following their injury (Marsh, Kersel, Havill, & Sleigh, 1998). Computer-mediated support groups (CMSGs) offer a virtual platform for individuals with complex medical concerns to exchange emotional and informational support (Braithwaite, Waldron, & Finn, 1999). To date, no research has examined the use of CMSGs, such as TBI-related Facebook support groups, for TBI survivors. There is also limited research investigating how emotional and informational support provided and received (i.e., supportive exchanges) relate to well-being and online relational health (Liang et al., 2002). This study examined the relationship between four supportive exchanges and well-being and relational health for TBI survivors using TBI-related Facebook support groups, as well as whether a gender norm—emotional control—and network preference moderated these relationships. Participants included 191 TBI survivors recruited across 14 TBI-related Facebook support groups. Multiple regression analyses tested whether four supportive exchanges directly predicted well-being and relational health after controlling for age and extraversion. Results revealed that supportive exchanges did not predict well-being. However, emotional support provided, emotional support received, and informational support received all predicted higher levels of online relational health. Informational support provided predicted lower levels of online relational health. Additional multiple regression analyses tested whether emotional control and four aspects of network preference moderated the relationship between supportive exchanges and well-being and relational health. Although higher levels of emotional control directly predicted lower levels of relational health, and a preference for weak-tie support networks (e.g., online acquaintances) predicted lower levels of well-being, the moderating effects were generally not significant. The findings underscore the importance of supportive exchanges in developing online relational health for TBI survivors using Facebook support groups. It also suggests that this relationship was not dependent on emotional control and network preference. Future research should investigate other factors affecting supportive online communication for TBI survivors and when they may benefit most from online support. / Thesis (PhD) — Boston College, 2018. / Submitted to: Boston College. Lynch School of Education. / Discipline: Counseling, Developmental and Educational Psychology.

Introduction: High intensity holistic neuropsychological rehabilitation is the most evidenced-based intervention for post-acute ABI rehabilitation. However, the majority of the current evidence has examined inpatient or residential treatment contexts. Little is known about the efficacy of community neuropsychological rehabilitation interventions or the clinical validity of both high and low intensity forms of rehabilitation in a community rehabilitation setting. The systematic review synthesises the existing evidence for community-based holistic neuropsychological rehabilitation and its psycho-social outcomes. Changes in self and group identity have been suggested to underpin evidence-based neuropsychological rehabilitation. However, little is known about how these processes of identity change following ABI and throughout the rehabilitation process. The empirical study explores key turning points in the self-narratives of individuals with ABI in order to better understand the clinical and contextual factors which influence their rehabilitation. Methods: A search was conducted of Embase, Embase classic, Medline and PsycInfo. Studies were assessed for risk of bias and outcomes were synthesised following the PRISMA guidelines for systematic reviews. A ‘holistic-content’ narrative methodology was then employed to explore the post-acute adjustment and rehabilitation narratives of 11 individuals following ABI. Three-dimensional analysis of interaction, continuity and situation was used to examine individuals’ personal reflections of identity changes across their illness experience; and cross-case comparisons identified common transformational themes. Results: 15 studies were included in the review. Two distinct levels of intervention intensity were identified: high intensity interventions delivered multiple days per week, and low intensity interventions delivered only once a week. A synthesis of nine studies examining high intensity neuropsychological rehabilitation found evidence that these interventions can improve psychological wellbeing and enhance community integration following ABI when delivered on an outpatient basis. A synthesis of six low intensity interventions found limited evidence that they can lead to improved psycho-social outcomes when structure to target specific difficulties, and evidence that they can effectively support the achievement of individual patient goals. Following the analysis of ABI survivor narratives, themes of ‘Rehabilitation focus and psychological distress’, ‘Reclaiming efficacy in valued life domains’, and ‘Social comparisons: inclusion and exclusion’ were identified; each representing a continuum of personal and social understanding along which people moved during their rehabilitation. Conclusions: The systematic review suggested that high intensity forms of outpatient neuropsychological rehabilitation are effective at improving psycho-social outcomes. Low intensity forms of outpatient neuropsychological rehabilitation appear to offer a less favourable alternative to supporting psycho-social adjustment in the community at present. Findings from the empirical paper suggest that illness identity may be co-constructed in the context of early treatment experiences, and appears to influence post-acute rehabilitation focus; and that pre-injury values and self-identity guided participant approaches to re-establishing self-efficacy. These processes were supported by clinical, social and group interactions.

O trauma crânio-encefálico contuso (TCEC) é freqüentemente seguido por um período de amnésia pós-traumática (APT), importante indicador da gravidade desse tipo de trauma e subsídio nas decisões sobre a reabilitação dessas vítimas. Considerando as diversas dificuldades que têm sido apontadas na literatura para estabelecer a duração da APT e algumas lacunas no conhecimento dessa síndrome, este estudo teve como objetivos: identificar os fatores relacionados à APT de longa duração (> 24 horas) entre as características apresentadas pelas vítimas de TCEC na fase aguda do trauma, comparar a qualidade de vida das vítimas que apresentaram APT de longa duração, com as demais e analisar a relação entre qualidade de vida e duração da APT, computando ou não o período de coma. Foi realizado um estudo prospectivo longitudinal, com abordagem quantitativa, descritiva correlacional, utilizando dados tanto da fase aguda de tratamento (internação hospitalar pós-trauma), como também da avaliação de qualidade de vida realizada entre três e seis meses após o evento traumático. Foram alvo desta investigação 187 vítimas de TCEC, com idade superior a 14 anos, sem diagnóstico anterior de demência ou TCEC, atendidas em Pronto-Socorro de hospital de referência para atendimento de trauma na cidade de São Paulo, nas primeiras 12 horas após evento traumático e internadas nesse hospital entre dezembro de 2006 e outubro de 2007. As variáveis independentes analisadas para identificar fatores associados a longo tempo de APT foram idade, sexo, gravidade do trauma crânio-encefálico, local e tipo de lesão, número de lesões encefálicas diagnosticadas e uso de medicação com atividade em sistema nervoso central ou corticóides. A maioria da casuística era sexo masculino (86,2%), vítimas de acidentes de trânsito (58,3%), com indicação de TCEC leve pela ECGl (61,5%). A média da idade foi 38 anos (± 16,81), da duração de APT foi 7,8 dias (±12,2), incluindo o tempo de coma e 5,0 dias (±6,7), sem incluir esse período. Os fatores associados a APT de longa duração, identificados em modelo de regressão logística ajustado pela variável área de lesão (intra/extra axial), foram: ECGl inicial <= 12 (OR= 20,17) MAIS/cabeça >=3 (OR= 2,80) e uso de Fenitína (OR= 2,60), Midazolan (OR=2,83) ou ambas as drogas (OR= 3,83). Quando comparada à qualidade de vida entre as vítimas que apresentaram APT de longa e curta duração, observou-se diferença significativa entre os grupos nos domínios Capacidade Funcional, Limitação para Atividades Físicas e Atividade Social da SF-36 Health Survey (SF-36). O grupo com APT de longa duração apresentou resultados mais desfavoráveis do que o de curta nesses três domínios. As análises de correlação entre domínios da SF-36 e duração da APT considerando ou não o tempo de coma indicaram que a medida do tempo de APT deve excluir o período coma, tendo em vista que as correlações foram mais expressivas quando essa forma de medida da APT foi utilizada / The closed traumatic brain injury (CTBI) is usually followed by a post-traumatic amnesia (PTA) period, important indicative of gravity to this kind of trauma and used to decisions for rehabilitation of the victims. Considering difficulties to establish the permanence of PTA in the available literature, as well as lack of knowledge of this Sindrome, this study had as main objectives: identify main points related to PTA of long term (> 24 hours) for CTBI victims during the hard period of trauma, compare victims\' quality of life for those who presented long term with those who doesn´t, and analysis the relationship between quality of life and PTA period, being the patients or not, in coma period. This is a quantitative study that was made using prospective, longitudinal and correlational approach, using data from both main intense phase of the treatment (pos trauma hospitalization) and quality of life valuation considered 3 to 6 months after the traumatic event. It was aim of this research 187 CTBI victims, with their age superior of 14 years old, with no demency diagnosis before the event or TBI, all attended by the emergency of a Refence hospital for trauma patients in São Paulo city, in their first 12 hours after the trauma and interned in this same hospital in the period of December 2006 and October 2007. The independent variables analysed to identify association points for the long term PTA was age, sex, brain encephalic trauma gravity, local and lesion kind, number of encephalic lesion diangosticated and medicament with action in the central neurologic system used or corticoids. The main patients were male (86.2%), victims from traffic accidents (58.3%), with indication of mild CTBI by GCS (61.5%). Age media of 38 years old (± 16.81), PTA period was 7.8 days (±12.2), including coma period and 5.0 days (±6.7), without including this period. Points associated with long term PTA, identified by logistic regression model adjusted by the variable of the lesion area (intra/extra axial), was: GCS initial <= 12 (OR= 20.17) AIS/head >=3 (OR= 2.80) and use of Fenitoin (OR= 2.60), Midazolan (OR=2.83) or both drugs (OR= 3.83). When compared to quality of life of the victims that presented PTA long and short term, it is seen significant difference in the groups observing domain, functional capacity, limitation for physical and social activities from the SF-36 Health Survey (SF-36). The group with long term PTA has presented worst results than the short term in these three domains. The related analysis made between domain of SF-36 and PTA time (duration) considering or not coma period of time has indicated that the measure of time from PTA must exclude coma period, as well as the studies and correlations were much more expressive when this measure of PTA was used

Background: Childhood Traumatic Brain Injury (TBI) has been identified as a crucial public concern, causing interrup-tion in children’s cognitive development, sometimes resulting in permanent impairment or even death. Hence documen-tation in health and school records regarding their functioning or environmental restrictions post injury, seems vital for the facilitation of communication between a child’s systematic and ongoing environment. Especially since children’s health has been described as a holistic construct comprised of psycho, social and physical well-being. Requiring continual inter-disciplinary and collaborative efforts over their course of development. Aim: To explore literature related to cognitive functioning and recommended support for children who have experienced a TBI, and how professional’s document their associated problems within medical and school records regarding activities in or outside the classroom. Method: A sys-tematic review, strictly comprised of empirical studies. Selected due to its sequential structural design for attainment of literature relevant to the research topic of choice and quality assessment procedures which enable reduction of threats to bias findings. Results: A total of 9 articles were yielded after quality assessment and depicted that. Reduced processing speeds in cognitive ability domains can be regarded as the default or baseline outcomes after a childhood TBI. Predictors within these different domains impacted their adequate academic, social function and varied depending on age at injury (2-4yrs or 4-8yrs), Injury severity (mild, moderate/severe), family function and time points. Early and severe TBI showed significant residual impairments across all time points, whilst the mild to moderate groups showed low to average func-tioning, as with the typical sample groups after two-year time points. Executive, attention skills impairment and post injury support within home and school settings. Showed to have the highest impact on both behaviours in, outside the classroom and academic performance. Documentation: Mainly biological and admission details were documented in the medical records. Within school records, all except one most recent study used either parental, teacher reports or direct measures to assess functioning of TBI affected children within school. Hereby a need for documentation of environmental factors within medical records, high quality transition of their TBI information within their school settings and continual docu-mentation of their progress or supports in school is required.

Magnetic Resonance Imaging (MRI) is the most prominent non-invasive technique used in clinical diagnosis and biomedical research. Its development as an imaging technique has been aided by contrast agents (CAs) which enhance contrast to noise ratio in the images. This dissertation deals with paramagnetic lanthanide- and superparamagnetic iron-based nanoparticles (NPs) which are potential CAs at clinical field of 3 T and a high field of 9.4 T. Chapter 1 provides a brief overview of colloidal nanoparticles, with an emphasis on their surface chemistry and magnetic properties for bio-applications. Chapter 2 employs europium as an optical probe to illustrate the contribution of inner, second and outer sphere relaxation towards longitudinal and transverse relaxivities of paramagnetic NP-based CAs. Chapter 3 investigates the positive and the negative contrast enhancement abilities and magnetization of paramagnetic NPs comprising a core of sodium dysprosium fluoride with a sodium gadolinium fluoride shell. Their surface chemistry is tuned to target prostate cancer specifically. The application of these NPs is further extended in Chapter 4 to track an intraneuronal protein called tau following mild traumatic brain injury. Chapter 5 deals with facile synthesis and long-term stability of superparamagnetic iron NPs for their potential application as CAs. Chapter 6 illustrates the concept of MRI correlation using ‘T1-only’ and ‘T2-only’ NPs. Chapter 7 investigates on the dynamics involved in the phospholipids coating the surface of NPs. Chapter 8 concludes on the work detailed in the previous chapters and outlines the future outlook. / Graduate / 2020-01-15

In the last decade, traumatic brain injuries (TBIs) and spinal cord injuries (SCIs) has become one of the most scrutinised medical challenges of our time. However, the lower quality of life experienced by the sufferer and the associated socio-economic cost of both TBI and SCI remain a huge burden for society. There is currently no reliable way to evaluate the level of functional damage caused by TBI and SCI related mechanical forces without invasive examination. The types of axonopathy involved in such injuries are the combinations of coupled mechanical-electrophysiological phenomena at multiple length and time scales, extremely challenging to approach by experimental means alone. It is therefore highly desirable to complement experimental studies with computational work to further the understanding of such multiscale problems. This thesis firstly proposes a novel 3D finite element framework coupling mechanics and electrophysiology to model cellular and subcellular phenomena, such as nerve dislocation and membrane damage by micropipette. The former study shows that 1D simulations focussing solely on the stretch component of the axonal damage are unable to capture the same electrophysiological damage that a 3D framework predicts. The latter study shows that local membrane deformation can lead to electrophysiological alterations at the axonal level solely through geometrical effects and without the need to account for ion channel activity alterations. This was demonstrated for micropipette suction in a patch clamp where the consideration of the 3D flow of current was sufficient to alter its electrophysiology, offering an alternative explanation to the damage mechanism hypothesised by published experimental work. At the axonal and tissue scale, previous models have often simplified the modelling of damage by using a single axon model. It is however unclear whether an altered axonal electrophysiology can truly be representative of the compound electrophysiology of multiple axons or fibre. Three different models: axonal, fibre and tissue level models, were evaluated and compared for their ability to model macroscale electrophysiology deficits. The results of the three models suggest that the recovery of compound action potential amplitude post-mechanical stretch can not be straightforwardly scaled from axonal level to fibre level. Furthermore, the electrophysiological recovery may not be solely dependent on mechanical recovery of the tissue. This thesis identified the need for scale specific models in the context of TBI and SCI. In particular, lipid bilayer membrane geometrical distortion following mechanical insult at the subcellular scale and functional tissue alteration at the tissue scale both require a different approach. The models proposed herein successfully identify mechanisms overlooked in previous experimental literature. In order to fully capture experimental behaviour, future models will need to account for other mechanisms such as mechanoporation, reorganisation of paranodal junctions and injury related Calcium ion imbalance.

Wearable assistive robotics have the potential to address an unmet medical need of reducing disability in individuals with chronic hand impairments due to neurological trauma. Despite myriad prior works, few patients have seen the benefits of such devices. Following application experience with tendon-actuated soft robotic gloves and a collaborator's orthosis with novel flat-spring actuators, we identified two common assumptions regarding hand orthosis design. The first was reliance on incomplete studies of grasping forces during activities of daily living as a basis for design criteria, leading to poor optimization. The second was a neglect of increases in muscle tone following neurological trauma, rendering most devices non-applicable to a large subset of the population. To address these gaps, we measured joint torques during activities of daily living with able-bodied subjects using dexterity representative of orthosis-aided motion. Next, we measured assistive torques needed to extend the fingers of individuals with increased flexor tone following TBI. Finally, we applied this knowledge to design a cable actuated orthosis for assisting finger extension, providing a basis for future work focused on an under-represented subgroup of patients.