Introduction: Socio-emotional behaviour difficulties following acquired brain injury (ABI) have been shown to have a persisting negative effect on quality of life. A systematic review was carried out to look at the efficacy and clinical effectiveness of available psychological treatments for socio-emotional behaviour difficulties following ABI. Research was carried out to further understand socio-emotional behaviour by exploring the possible underlying cognitive aspects (specifically social cognition) in a traumatic brain injury (TBI) population. The study investigated the relationship between social cognition and socio-emotional behaviour post-TBI. Method: A systematic search of articles published between January 2008 and November 2013 was carried out following the Cochrane (2008) guidelines. Papers were quality assessed to identify strengths and weaknesses. In the research study, forty TBI participants were asked to complete tasks of emotion recognition, theory of mind, cognitive flexibility, processing speed, attention and working memory. Selfrated and proxy-rated behaviour questionnaires were also administered. Results: The systematic review revealed seven studies for inclusion; three papers looked at a Comprehensive Holistic Approach, two papers on Cognitive Behavioural Therapy, and two on Cognitive Rehabilitation Therapy. The findings suggested that CHA showed the best efficacy and generalization. However, there were also positive results within the CBT studies. The research paper found that the TBI group performed significantly poorer than the control group on measures of emotion recognition and three out of the four ToM tasks. The TBI group also performed significantly poorer on measures of processing speed and working memory (executive function). There was no association found between performance on any of the cognitive tests and socio-emotional behaviour. Conclusions: This is an area of limited research, likely due to the challenges of carrying out research in an ABI population. The systematic review highlighted the limited research available which has implications in clinical practice due to a lack of evidence base for potentially effective interventions. The research study results suggest that there is still a lack of understanding of socio-emotional behaviour and its underlying cognitive functioning. Further research would improve understanding and could also focus appropriate post-ABI interventions for socio-emotional behaviour problems.

Fundação de Amparo a Pesquisa no Estado do Rio Grande do Sul / This study presents an analysis on the effects of creatine supplementation on parameters of susceptibility to seizures induced by subconvulsant dose of pentylenetetrazol (PTZ) in an experimental rat model of traumatic brain injury (TBI). TBI is an acute neurological event that can lead to chronic neurological disease, such as epilepsy. Given the magnitude of the problem, various forms of therapy is being tested, but many have failed and yet, few take into account the susceptibility to seizures as an outcome and concentrate on a very early period of injury, getting away from the reality of patients in underdeveloped countries. Creatine is an interesting compound to be evaluated for this purpose, since it has neuromodulatory properties and may regulate synaptic plasticity in developing neurons. Thus, it became interesting to investigate whether there is any effect of creatine in this scenario. To this, creatine supplementation was held by gavage in rats subjected to fluid percussion TBI model and this supplementation began one week after TBI, once a day for four weeks. PTZ test was performed two hours after the last dose of creatine. Furthermore a similar protocol was performed to verify the persistence of the effect and secondly, to verify the acute effect of creatine, just before the PTZ test. Latency for myoclonic and tonic clonic seizures, total time of generalized seizure as the clinical severity through the scale of Racine were measured and also epileptiform discharges and spindle activity before and after the administration of PTZ were quantified. As main results, it was found a decreased susceptibility to seizures in rats supplemented by a month, and the effect remained even if there was withdrawal of creatine for a week, however, this effect was not observed in the single dose of the compound. Still, a positive correlation between epileptiform discharges and spindle activity was found, both reduced in animals supplemented continuously. Thus, creatine is presented as a candidate to be tested in studies with TBI, with the purpose of reducing the susceptibility to seizures. / Este trabalho apresenta uma análise dos efeitos da suplementação de creatina sobre parâmetros de suscetibilidade à crise epiléptica induzida por pentilenotetrazol (PTZ) em dose subconvulsivante, por modelo experimental de traumatismo cranioencefálico (TCE) em ratos. O traumatismo cranioencefálico (TCE) é um evento neurológico agudo que pode levar à doença neurológica crônica, como a epilepsia. Devido a magnitude do problema, diversas formas terapêuticas vêm sendo testadas, porém muitas falharam e ainda, poucas levam em conta o desfecho da suscetibilidade à crises epilépticas, além de se concentrarem em um período muito precoce da patologia, ficando longe da realidade dos pacientes de países subdesenvolvidos. A creatina consiste num interessante composto a ser avaliado para esse fim, já que apresenta propriedades neuromodulatorias e de regulação da plasticidade sináptica em neurônios em desenvovlimento. Assim, tornou-se interessante investigar se existe algum efeito da creatina nesse cenário. Para isso, realizou-se suplementação de creatina por gavagem em ratos submetidos ao TCE por percussão de fluído, iniciada esta suplementação uma semana após o TCE, uma vez ao dia, por quatro semanas, sendo o teste com PTZ realizado duas horas após a última dose. Também foi realizado um protocolo semelhante para verificar se o efeito da creatina era duradouro e outro, para verificar o efeito agudo, logo antes do teste com PTZ. Foram mensurados o tempo de latência para crises mioclônica e tônico clônica generalizada, tempo total de crise generalizada, gravidade da crise através da escala de Racine, bem como quantificada as descargas epileptiformes e ondas de fuso antes e após a administração de PTZ. Como resultados principais, encontrou-se a diminuição da suscetibilidade à crises epilépticas nos ratos suplementados por um mês, e o efeito permaneceu mesmo quando houve retirada da creatina por uma semana adicional, porém, esse efeito não foi observado na administração única do composto. Também houve correlação positiva do aparecimento de descargas epileptiformes e atividades de fuso, ambas reduzidas nos animais suplementados continuamente. Assim, a creatina apresenta-se como substância candidata à testes em estudos com traumatismo cranioencefálico, com a finalidade de diminuir a suscetibilidade à crises epilépticas.

Traumatic brain injury (TBI) is the leading cause of death and disability among children and adolescents. Brain injury survivors are often left with persistent impairments that have the potential to impede daily functioning, delay or prevent the attainment of developmental milestones, and subsequently limit future productivity in adulthood. A shared goal of both neurorehabilitation and the educational system is to prepare youth for a productive adulthood with both systems of care having substantial, yet independent, literature bases regarding factors associated with productivity (e.g., engagement in employment or post-secondary education). It is currently assumed that because type of high school exiting (e.g., diploma, GED, dropout) is related to productivity for the general population, it also is related to productivity for adolescents with a serious TBI. It is possible that the factors outlined in the TBI literature account for the majority of the variance in this relationship and that exiting has no unique relationship with future productivity for this neurologically compromised population. As such, the purpose of this study was to explore the intersection of TBI and high school exiting. This study was a secondary analysis of the Traumatic Brain Injury Model Systems (TBIMS) database and featured a sample (n = 202) of 16 to 18-year-olds who were enrolled in high school when they sustained a moderate to severe TBI and subsequently attended inpatient neurorehabilitation. All participants in this study suffered their injuries between 4/1/2003 and 10/1/2010. The first aim of this study was to describe the rates of high school exiting for students with a moderate or severe TBI who attended inpatient neurorehabilitation and to examine group differences (e.g., race, insurance type, injury severity). Currently, there are no known data regarding rates for type of high school exiting (diploma, GED, dropout) or group differences for this population. This study found rates of 83% diploma, 5% GED, and 12% dropout. These rates are striking as they mirror data reported for the general student population. When examining group differences, several factors appeared to be more likely associated with earning a diploma (i.e., White, not receiving Medicaid, no pre-injury learning problem, no pre-injury learning problem, injury severity, higher motor functioning at rehabilitation discharge, acute length of stay) and others with GED (i.e., pre-injury learning problem, pre-injury substance use problem) or dropout (i.e., nonWhite, receiving Medicaid, pre-injury learning problem, lower cognitive functioning at rehabilitation discharge). In this study, variables associated with diploma were conceptualized as protective factors and variables associated with dropout conceptualized as risk factors. Findings from aim one (rates, group differences) are foundational data regarding high school exiting for students with a TBI. These data have the potential to provide normative reference, instill hope, spur collaboration between medicine and education, provide targets for intervention and policy, and serve as the foundation for future research. The second aim of this study was to examine if exiting type has a unique relationship with future productivity. Productivity was defined as hours per week engaged in post-secondary education and/or employment. Results indicated that exiting type (i.e., diploma) had a unique relationship with total productivity and educational productivity but not employment productivity after TBI. Employment productivity was better explained by several established predictors of productivity (race, pre-injury special education status, post-traumatic amnesia, functioning at rehabilitation discharge). The data from this study provide preliminary evidence that for students who attend inpatient neurorehabilitation after a serious TBI, earning a diploma is attainable, successful exiting can be promoted, and that earning a diploma is related to outcome (i.e., productivity). Overall, findings from this study provide foundational data that have the potential to aid in prognostication, serve as targets for intervention, and deserve further scientific inquiry.

Abstract Head injury is the leading cause of death and disability in trauma patients, and alcohol misuse is often associated with such injuries. Despite modern diagnostic facilities, the extent of traumatic brain injury (TBI) is difficult to assess and supplementary diagnostic tools are warranted. The contribution of alcohol misuse to traumas also needs to be elucidated, as the role of different patterns of alcohol drinking in particular has received less attention. We investigated the clinical utility of a novel serum marker of brain damage, protein S100B, as a tool for assessing TBI in patients with trauma. We also investigated the patterns of alcohol drinking among trauma patients and the trauma mechanisms in relation to blood alcohol concentration (BAC), with special emphasis on head traumas. Finally, we studied the early identification of hazardous drinkers among trauma patients. Serum protein S100B was found to be a feasible supplementary method for assessing TBI, as the latter was shown to elevate its levels significantly, the highest values being found in patients with severe injuries. S100B was also found to be elevated in patients with mild head injury, where it was associated with an increased risk of developing post-concussion symptoms (PCSs). Extracranial injuries also increased S100B values in patients with multitrauma. Accordingly, S100B was not specific to TBI. The more severe the extracranial injury, the higher the S100B value that was found. Binge drinking was found to be the predominant pattern in trauma patients. Alcohol intoxication on admission and hazardous drinking patterns were more often present in patients with head injury than in those with other types of trauma. The risk of sustaining a head trauma significantly increased with increasing BAC. The results also demonstrated that BAC on admission is the best marker of alcohol misuse in trauma patients. The BAC test depicts hazardous alcohol drinking better than conventional biochemical markers of alcohol misuse such as gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), carbohydrate-deficient transferrin (CDT), or mean corpuscular volume (MCV) of erythrocytes. The findings support the use of S100B as a supplementary method for assessing TBI and the use of BAC as a marker of alcohol misuse in trauma patients.

L'objectif principal de cette thèse était de déterminer la prévalence des antécédents de traumatisme crânien dans une population de détenus. Les objectifs secondaires étaient de déterminer les co-facteurs pouvant influencer le parcours pénal en cas d'association avec un antécédent de traumatisme crânien. Une revue systématique de la littérature a retrouvé une prévalence moyenne calculée d'antécédents de traumatisme crânien de 46%. Une enquête épidémiologique descriptive a inclus 1148 arrivants en prison à Fleury-Mérogis. La prévalence d'antécédents de traumatisme crânien était de 30,6%. L'analyse des résultats pour la population masculine adulte a mis en évidence que les personnes déclarant un antécédent de traumatisme crânien ont passé plus de temps en prison et ont fait plus de séjours en prison durant les 5 dernières années. Ils avaient également une santé perçue moins bonne. Ils étaient plus nombreux à déclarer une épilepsie, un suivi psychiatrique, une consommation d'alcool, de cannabis et de médicaments psychotropes. Dans la population féminine, la santé perçue était plus mauvaise et la consommation d'alcool était plus fréquente en cas d'antécédent de traumatisme crânien. La comparaison entre hommes et femmes ayant déclaré un traumatisme crânien n'a pas retrouvé de différence en dehors d'une santé perçue plus mauvaise pour les femmes et d'une consommation de cannabis plus importante pour les hommes. L'analyse la population des mineurs est en cours. Ces résultats amènent un certain de nombre de propositions pour la prise en charge médicale et sociale de cette population. / The main objective of this thesis was to estimate the prevalence of traumatic brain injury in a population of incomers in prison. A further aim was to study co-variables that can have an impact on criminality when associated with a history of traumatic brain injury. A systematic review was performed to estimate an average prevalence of history of traumatic brain injury, which was found to be 46%. Then, a descriptive epidemiological study, which included 1,148 incomers in prison, was carried out at Fleury Merogis prison. The prevalence of history of traumatic brain injury was 30.6%. Among the adult male population, males who declared a history of traumatic brain injury spent more time in prison and came more often in prison during the past 5 years. They also declared a worse perceived health. They were more likely to report an epilepsy, psychiatric care, alcohol, cannabis and psychotropic drugs use. Among females, perceived health was worse and alcohol consumption was more common for females with a history of traumatic brain injury. When comparing males and females who declared a history of traumatic brain injury, no difference was found except a worse perceived health for women and a greater use of cannabis for men. The analyses regarding juveniles are still ongoing. These results provide further evidence that a number of measures have to be developed regarding medical and social care for this population.

Class of 2011 Abstract / OBJECTIVES: The overall purpose of this study was to describe comorbidities, charges, and mortality associated with inpatient, adult traumatic brain injury (TBI) cases in the United States (US) for the year 2007. METHODS: This was a retrospective cohort analysis of discharge records located in the National Emergency Department Sample (NEDS) of the Healthcare Cost and Utilization Project (HCUP). Descriptive statistics are provided for comorbidities, charges, and mortality. Logistic regression was performed to find characteristics associated with mortality while multiple regression was used to assess charges. Independent variables included age, injury severity, procedures used, location of TBI, and primary payer. RESULTS: A total of 639,698 TBI cases were found which were associated with 267,061 hospital admissions, over $17 billion in hospital charges, and 20,620 deaths in the year 2007.Most common comorbidities were essential hypertension, sprains and strains of the back, tobacco use, fluid and electrolyte disorders, and alcohol-related disorders. Characteristics associated with increased mortality and charges included New Injury Severity Score (NISS) over 10, involvement of a firearm, falls, motor vehicle traffic, and intubation. CONCLUSION: The current study gives the most current picture of inpatient adult TBI cases throughout the US. Future research is warranted to ensure that optimal outcomes are being attained in this vulnerable patient population.

Mild Traumatic Brain Injuries (mTBIs) are non-penetrating brain injuries that do not result in gross pathological lesions, yet they may cause a spectrum of cognitive and behavioral deficits. mTBI has been placed in the spotlight because of increased awareness of blast induced and sports-related concussions, but the underlying pathophysiological mechanisms are poorly understood. Several studies have implicated neuronal membrane poration and ion channel dysfunction as the primary mechanism of injury. We hypothesized that injury forces utilize mechanically-sensitive, transmembrane integrin proteins, which are coupled to the neuronal cytoskeleton (CSK) and distribute injury forces within the intracellular space, disrupting CSK organization and reducing intercellular neuronal functionality. To test this, magnetic beads were coated with adhesive protein, allowing them to bind to integrins in the neuronal membrane in vitro. To apply forces to the neurons via the bound beads, we built custom magnetic tweezers and demonstrated that focal adhesions (FACs) formed at the site of bead binding. We showed that the beads were coupled to the CSK via integrins by measuring the disparate adhesion of the soma and neurite to their underlying substrate. The soma also required more force to detach than neurites, correlating with the FAC density between each neuronal microcompartment and substrate. We then utilized the magnetic tweezers to test whether beads bound to integrins injured neurons more than beads that bound to neurons nonspecifically. Integrin-bound beads injured neurons more often and the injury was characterized by the formation of focal swellings along axons, reminiscent of Diffuse Axonal Injury. While integrin-bound beads initiated swellings throughout neurons, beads bound nonspecifically only caused local injury where beads were attached to neurons. To demonstrate the electrical dysfunction of integrin-mediated injury forces, we adapted Magnetic Twisting Cytometry to simultaneously apply injury forces to beads bound to multiple cells within neuronal networks in vitro. The formation of focal swellings resulted in reduced axonal electrical activity and decreased coordinated network activity. These data demonstrate that the mechanical insult associated with mTBI is propagated into neurons via integrins, initiating maladaptive CSK remodeling that is linked to impaired electrical function, providing novel insight into the underlying mechanisms of mTBI. / Engineering and Applied Sciences

Traumatic Brain Injury (TBI) is linked to a diverse range of diffuse pathological damage for which there is a severe lack of therapeutic options. A major limitation to drug development is the inability to identify causal mechanisms that link head trauma to the multitude of secondary injury cascades that underlie neuropathology. To elucidate these relationships, it is important to consider how physical forces are transmitted through the brain across multiple spatial scales ranging from the whole head to the sub-cellular level. In doing so, the mechanical behavior of the brain is typically characterized solely by its material properties and biological structure. Alternatively, forces transmitted through distinct cellular and extracellular structures have been shown to influence physiological processes in multiple cell types through the transduction of mechanical forces into cellular chemical responses. As an essential component of various biological processes, these mechanotransduction events are regulated by mechanical cues directed through extracellular matrix (ECM) and cell adhesion molecules (CAM) to mechanosensitive intra-cellular structures such as focal adhesions (FAs). Using a series of in vitro models, we have implicated FAs in the cellular mechanism of traumatic axonal injury by showing that forces directed through these structures potentiate injury levels and, moreover, that inhibition of FA-mediated signaling pathways may be neuroprotective. In addition, we show that localizing trauma forces through specific brain ECM results in differential injury rates, further implicating mechanosensitive cell-ECM linkages in the mechanism of TBI. Therefore, we show that FAs play a major role in axonal injury at low strain magnitudes indicating that cellular mechanotransduction may be an important mechanism underlying the initiation of cell and sub-cellular injuries ultimately responsible for the diffuse pathological damage and clinical symptoms observed in diffuse axonal injury. Furthermore, since these mechanisms may present the earliest events in the complex sequelae associated with TBI, they also represent potential therapeutic opportunities. / Engineering and Applied Sciences

Objectives: The majority of individuals who sustain a mild traumatic brain injury (mTBI) will experience a full recovery within the first weeks or months post-injury. However, some individuals will experience ongoing difficulties, or persistent post-concussion symptoms (PCS), for years following the injury. To date, most researchers have attributed PCS to either neuropathological factors or to psychogenic factors. Lacking exploration has been the role of psychosocial variables and the consideration of PCS from a more holistic, or 'whole person', perspective. As such, the goal of the current study was to undertake an investigation of persistent PCS using a broad, neuropsychosocial framework. Specifically, this was done by investigating how (a) cognitive functioning, (b) susceptibility to anxiety while in the context of a stressful situation (i.e., anxiety susceptibility), and (c) multiple components of identity (including self-perception, TBI- related self-concept, and TBI-related social identity) influence the severity of persistent PCS. The main underlying assertion to this research is that there are multiple factors that underlie the experience of persistent PCS; a purely neuropathological or psychogenic perspective is not sufficient to understand the complex processes inherent in recovery after mTBI. Method: The sample consisted of 21 adults, between 20 and 65 years of age, who had sustained an mTBI at least one year earlier. Following a telephone interview to determine eligibility (and a separate telephone interview with a source of collateral information) the participants completed a number of standardized neuropsychological measures and self- report questionnaires during an in-person, one-on-one data collection session. Results: The only injury-related or demographic variable that had an influence on PCS was injury etiology, whereby individuals with sports related injuries reported significantly less PCS than did those who sustained non-sports related injuries (e.g., motor vehicle accidents). Cognitive functioning had no influence on PCS severity, nor did anxiety susceptibility. However, one's general propensity to experience anxiety (i.e., trait anxiety) was a significant predictor of PCS. Further, multiple aspects of identity influenced PCS with both current self-perception and TBI-related social identity being significant predictors of self-reported PCS severity. Conclusions: Despite the failure to find any impact of neuropsychological factors on PCS in the current study, other lines of research have demonstrated neuropathological changes associated with mTBI – some of which may be chronic. Therefore, cognitive functioning may not be a sufficiently sensitive indicator of possible neuropathology at more than one year post-injury. On the other hand, the current study demonstrates that psychological and psychosocial factors are highly relevant to recovery and outcome following mTBI, and are significant predictors of PCS severity. Overall, the results support the assertion that recovery after mTBI is complex and that there are multiple factors that underlie persistent PCS. Further, the study demonstrates the importance of conceptualizing the process of recovery from a broad, neuropsychosocial perspective. Implications for treatment interventions and future research are discussed. / Graduate

The long-term consequences of repetitive mild traumatic brain injuries (mTBIs), or concussions, as well as the immediate acute dangers of head collisions in sport have become of growing concern in the field of medicine, research and athletics. An estimated 3.8 million sports-related concussions occur in the United States annually, with the highest incidence having been documented in football, hockey, soccer, basketball and rugby (Harmon et al., 2013). The incidence of concussion in the National Rugby League (NRL) corresponds to approximately 8.0-17.5 injuries per 1000 playing hours, with tackling having been identified as the most common cause (Gardner et al., 2014; King et al., 2014). The highest incidence of rugby concussive impacts is a result of shoulder-to-head collisions (35%) during tackles and game play (Gardner et al., 2014). Shoulder-to-head concussive events occur primarily on the ball carrier and secondarily on the tacklers (Hendricks et al., 2014; Quarrie & Hopkins, 2008). While some studies report that the ball carrier is at a greater risk of sustaining a concussion (Gardner et al., 2015; King et al., 2010, 2014), others have demonstrated a greater incidence of tacklers being removed from play for sideline concussion evaluation (Gardner et al., 2014). Given this discrepancy, the purpose of this study was to compare dynamic response and brain tissue deformation metrics for ball carriers and defensive tacklers in professional rugby during shoulder-to-head concussive impacts using in-laboratory reconstructions. Ten cases with an injured defensive tackler and ten cases with an injured ball carrier were reconstructed using a pneumatic linear impactor striking a 50th percentile Hybrid III headform to calculate dynamic response and maximum principal strain values. There was no significant difference between the two impact conditions for peak resultant linear and rotational accelerations, as well as brain tissue deformation. Differences between metrics in this research and past research where the impacting system was not reported were discussed. These differences reflect the importance of accounting for impact compliance when describing the risk associated with collisions in professional rugby.