Very little is known about the effects of paediatric traumatic brain injury (TBI) on prospective memory, the memory for future intentions such as remembering to post a letter in the morning or do homework. The main aim of this thesis was to redress that shortcoming in the literature. To investigate the effects of paediatric TBI on prospective memory as reliably and fully as possible, the study of children and adolescents with brain injuries was preceded by a developmental study. Given that the process of recovery from brain injury is imposed on the ongoing process of development, it is important to understand more about the normal developmental trajectory of prospective memory first of all. Study 1 compared the prospective-memory performance of 88 normally developing children, adolescents and young adults. The main task was computerised, and its design was influenced by a prefrontal-lobe model because prospective memory is believed to be mediated by the prefrontal regions of the brain. Variables associated with prefrontal-lobe capacity were manipulated: the cognitive demand of an ongoing task, and the importance of the prospective task. Results of Study 1 found that children remembered to respond to fewer prospective cues than adolescents or adults, but that adolescents and adults remembered similarly. Further, the differences between the children's performance and the adolescents' and adults' widened as the cognitive demand of the ongoing task increased. However, the effects of increasing the cognitive demand did not vary between the adolescents and adults. It made no difference to anyone's performance whether the importance of remembering the prospective cues was stressed or not. On the other hand, performance on executive functions, as measured by the Self-Ordered Pointing Task (SOPT), the Stroop Colour Word Interference Test (Stroop), and the Tower of London (TOL), which are also believed to be affected by prefrontal capacity, produced the same age effects as were produced on the computerised prospective-memory task. Further, performance on the SOPT and Stroop predicted performance on the high-demand level of the prospective-memory task. Study 2 compared 34 children and adolescents with TBI with the non-injured children and adolescents from Study 1 on the same tasks. Results revealed that overall those with TBI had poorer prospective-memory performance than their non-injured peers. However, a different pattern of impairment was evident in the children than in the adolescents. Specifically, the children with TBI performed similarly to their non-injured peers, but the adolescents with TBI were significantly worse than the non-injured adolescents. This trend was most noticeable as the cognitive demand of the ongoing task increased. Further, the age and injury effects were reflected in the performances on the executive-function tests, and the TOL predicted performance on the high-demand, prospective-memory task in those with TBI. Study 3 aimed to examine the ecological validity of Study 2, by investigating whether the impairments in prospective memory in young people with TBI measured quantitatively, were matched with qualitative data. Twelve parents of children and adolescents with mild to severe TBI were interviewed about whether or not their children's injuries impacted on their memory (retrospective and prospective) in everyday life. Results showed that in general most children suffered memory losses as a result of their brain injuries, and that prospective-memory loss caused particular hardships for the children and their families. Taken together, the results of the current research revealed that the development of prospective memory reaches a peak of maturity in adolescence, and that adolescents with TBI show greater decrements in prospective memory than adolescents without TBI, but that this pattern is not evident in children, where those with TBI were not significantly different from those without. These findings give support to the prefrontal-lobe model of prospective memory by showing that prefrontal maturity, which reaches a peak during adolescence, reflects the prospective-memory performance of healthy adolescents, and prefrontal injury, which is very common with TBI, shows the effects of deficits more during adolescence than in earlier years when the prefrontal regions are not yet fully developed. Study 3 showed that impairments in prospective memory that result from TBI translate into disabilities in the real world. As a follow up it is recommended that rehabilitation strategies be designed to assist young people with prospective-memory impairments adjust better to school and the demands of everyday living. The prefrontal-lobe model should guide the design of such strategies.

Hyper-activation of N-methyl-D-aspartate receptors (NRs) is associated with excitotoxic cell death during secondary injury following traumatic brain injury (TBI). The efficiency of the NR is dependent on the location of receptors in membrane raft microdomains that provide a platform for coupling of NRs and effector proteins. In many neurodegenerative diseases, activation of the autophagy pathway has been suggested to contribute to glutamate excitotoxicity, but whether increased autophagy signaling contributes to pathology after TBI has not been defined. In these studies, I investigate whether membrane rafts mediate NR signaling and autophagy in cortices of adult male rats subjected to moderate TBI and in sham-operated controls. These studies demonstrate that membrane rafts of the normal rat cortex contain a novel multi-protein signaling complex that links the NR2B glutamate receptor and the autophagic protein Beclin 1. TBI caused a rapid disruption of this complex in which NR2B and pCaMKII were recruited to membrane microdomains. Alteration in NR2B-Beclin 1 association in membrane rafts resulted in activation of autophagy as demonstrated by increased expression of key autophagic proteins Beclin 1, ATG 5 and ATG 7, and significant increases in autophagic vacuoles in neurons of traumatized brains. Administration of the NR2B antagonist RO 25-6981 significantly blocked TBI-induced redistribution of NR2B signaling intermediates and Beclin 1 and delayed the increase in autophagy protein expression in traumatized cortices. Thus, stimulation of autophagy by NR2B signaling may be regulated by redistribution of Beclin 1 in membrane rafts after TBI.

La patología de origen traumático, cuarta causa de mortalidad y primera en cuanto a años perdidos, es un relevante problema de salud, que ocasiona además una elevada morbilidad e incapacidad y un alto coste sanitario y social. El conocimiento de su abordaje se ha realizado mediante el análisis de bases de datos de pacientes y encuestas a profesionales. El presente trabajo de investigación va dirigido a conocer si la asistencia al paciente adulto con TCE en las UCI catalanas de referencia para esta patología es comparable en cuanto a epidemiología, abordaje y resultados, a los que muestra la literatura referente a otros países de nuestro entorno. Se planteó un estudio con un objetivo principal doble, por un aparte describir las características demográficas y clínicas de los pacientes y por otro analizar el abordaje terapéutico y la monitorización. Como objetivos secundarios se plantearon conocer la variabilidad de los apartados anteriores según la gravedad del TCE, conocer si la práctica clínica se adhería a las principales recomendaciones de las Guías de Práctica Clínica vigentes y conocer el resultado neurológico final de los pacientes, identificando las posibles variables epidemiológicas estudiadas que pudieran influir en el resultado neurológico y la presencia de de insultos secundarios que se producen. Se realizó un estudio observacional, multicéntrico y prospectivo en las 7 UCIs catalanas de referencia para esta patología. Se recogieron datos demográficos, clínicos, radiológicos, monitorización, terapéuticos, complicaciones y de resultado de los pacientes que ingresaban en una UCI afectos de un TCE, con o sin politraumatismo durante los primeros 15 días de estancia. Se incluyeron pacientes 370 pacientes durante un año.Los principales resultados muestran un predomina el sexo masculino, edad media de 40 años, causa principal el accidente de tráfico. Un 36% de los casos ingresaron directamente en el centro de referencia pero únicamente el 26% en los primeros 60 minutos. El perfil de gravedad del TCE fue un 53% Graves, 27% Moderados y 20% Leves, con una lesión encefálica predominante tipo II de Marshall (39%). La presencia de HSA fue del 49%. Se monitorizó la PIC en el 69% de los TCE grave, la SjO2 en el 27% y el DTC en el 50%. La intensidad de la monitorización y el uso de la terapéutica se incrementa de acuerdo a la mayor gravedad del paciente. Hay una alta adherencia para las recomendaciones de las guías de práctica clínica en lo que hace referencia a la utilización de monitorización sistémica y neurológica, la utilización de barbitúricos, y menor en cuanto a la utilización de corticoides, e hiperventilación. La tasa global de mortalidad en UCI fue del 22%, un 31 % para los graves. Las variables explicativas de "éxitus" fueron el estado de las pupilas, el tipo de lesión radiológica, el sexo y la gravedad del TCE. La presencia de complicaciones prehospitalarias (hipoxia, hipotensión, broncoaspiración, paro cardiorrespiratorio, hipotermia o convulsiones) se constata en el 15% de los pacientes y se asocia de forma acumulativa con un mal resultado.Como conclusión general este trabajo de investigación apoya la hipótesis inicial de que la atención al TCE en las UCI catalanas estudiadas es comparable en cuanto a epidemiología, abordaje y resultados, a los que muestra la literatura referente a otros países de nuestro entorno. Palabras clave:Head injury, traumatic brain injury, neurocritical care. / Trauma disease represents the fourth cause of mortality in frequency and the first one in terms of lifetime waste. It constitutes a significant health problem that provokes a high morbidity and incapacity in addition to striking health and social costs. Since now, its management approach has been done through patient data bases analysis and surveys directed to professionals. This research report attempts to elucidate epidemiologic, management and clinical results' comparability between actual adult BTI clinical practice in Catalan ICU's, which are of reference for this pathology, and practice shown in medical literature in our environment. The study was planned with a double main objective; for one part, to describe demographic and clinical patient characteristics, and for the second part, to analyse patient monitoring and therapeutic management. As secondary objectives we proposed to explore variability by BTI clinical severity, adherence rate to recommendations addressed in Clinical Practice Guidelines in force, and patient neurological outcome, identifying those epidemiologic parameters probably influencing neurological outcome, apart from secondary insults incidence. An observational and prospective study was conducted in 7 reference ICU's in Catalonia. Patient data collected covered demographic, clinical, radiological, monitoring and therapeutic aspects, besides complications and outcome variables for patients that were admitted in the ICU with a BTI diagnosis, with or without multiple trauma, that were followed in their length of stay for a 15-day period. A total of 370 patients were included in the study period of 1 year.Main results show a predominance of males with a mean age of 40, being traffic accident the main cause of BTI. 36% were directly admitted to the reference hospital, but only 26% were admitted in the first hour after the accident. The BTI severity profile was: 53% severe, 27% moderate and 20% mild, being the highest prevalence (39%) type II Marshall encephalic injury. The existence of SH was 49%. ICP was monitored in 69% of severe patients and SjO2 in 27% and TCD in 50%. Monitoring and therapeutic use was shown to increase depending on the higher patient severity. Close adherence to clinical guidelines recommendations was proven for systemic and neurological monitoring and barbiturate use, and was lesser the adherence for hyperventilation and corticoid utilization. ICU mortality rate was 22%, raising 31% for severe patients. Dependent variables for mortality were found to be pupil status, type of radiological finding, sex and BTI severity. Pre-hospital complications (hypoxia, hypotension, bronchial aspiration, cardiac arrest, hypothermia, convulsions) were found in 15% of patients, and are cumulative associated with a worse outcome.As a general conclusion, this research report supports the initial hypothesis that BTI clinical practice reviewed in reference Catalan ICU's, is comparable to practice in other countries of our environment, as is shown from the medical literature published.

Moderate and severe pediatric traumatic brain injuries (TBI) are associated with significant familial stress and child cognitive and adaptive sequelae (Taylor et al., 1999). Research has demonstrated a relationship between familial stress and resources and child recovery of functioning following TBI (Taylor et al., 1999). We built on these findings by examining authoritarian parenting values and styles as a mediator of the relationship between parental stress and child adaptive outcomes 12-36 months following TBI or orthopedic injury (ORTHO). Participants were 21 children/adolescents with traumatic brain injuries and 23 with orthopedic injuries and one of their parents/guardians. Parents completed measures of demographics, parental stress, parenting values and styles, and child adaptive functioning. Child participants completed brief demographic questionnaires and intelligence screeners. Moderation was examined using hierarchical multiple regression. Mediation and moderated mediation were examined using bootstrapping tests of the indirect effect of parental stress on child adaptive functioning. After controlling for family insurance status, higher levels of parental stress were associated with reduced child adaptive functioning in the TBI group but not the ORTHO group. An examination of the mediational analyses revealed that higher levels of parental stress were associated with a greater reliance on authoritarian parenting styles, which was associated with reduced overall adaptive functioning and daily living skills across the two injury groups. Therefore, across groups, the relationship between parental stress and child overall adaptive functioning and daily living skills was found to be partially mediated by an authoritarian parenting style. Moderated mediation results revealed the presence of a significant interaction and 95% confidence interval on the socialization domain and indicated that the relationship between authoritarian parenting styles and child adaptive social skills differed significantly between the two groups. Our findings suggest a relationship between parental stress, authoritarian parenting styles, and child adaptive functioning in the 12-36 months following pediatric traumatic injury. Future research should explore the association among these, as well as other potentially mediating variables, both within and between the two groups with the goal of further elucidating the relationship between familial/environmental variables and child adaptive functioning following traumatic brain and orthopedic injury.

Traumatic brain injury (TBI), also referred to as an acquired brain injury, is caused by damage to the brain as a result of trauma to the head. The following report serves as a resource for patients and families wanting to gain information regarding community integration outcomes after participation in post-acute rehabilitation programs. The goal of the post-acute level of medical care is to increase functionality and serve as a transition for the patient from the rehabilitation facility to life within the community. A thorough examination of community integration after participation in a post-acute rehabilitative program with the use of the Community Integration Questionnaire (CIQ) is provided. After investigation of the available literature, four articles were found to meet inclusion criteria and were included within the review. All studies included met the following criteria. Participants were ages 17 to 65 years old, had a diagnosis of moderate to severe TBI, were enrolled in post-acute rehabilitation, and were assessed with the Community Integration Questionnaire (CIQ). Overall, the available literature suggests that completion of a program within a post-acute facility does create positive outcomes for the individual with TBI; however, the outcomes are dependent on various factors regarding TBI severity, the administration of intervention, the type of intervention, time post-onset and age of participants at the time of onset. Future research is necessary to provide a more comprehensive view of post-acute rehabilitation and the outcomes that these patients may expect as they begin their road to recovery. / text

This report provides an overview of the adverse effects of the antiepileptic drug topiramate. Specifically, it evaluates the negative cognitive-communication effects of topiramate on individuals with epilepsy and postulates that treating these deficits is within the scope of practice of speech-language pathologists. It begins with a discussion on epilepsy, description of seizures, and the mechanism of action for antiepileptic drugs. It then provides an overview of cognitive communication deficits caused by antiepileptic drugs, including: memory problems, impairments in attention, and executive dysfunction. The final section provides an outline of potentially beneficial treatments a speech-language pathologist may provide to patients experiencing adverse effects from topiramate and how continued research can expand this area of practice. / text

A novel cell culture system was designed to serve as a model of neuroinflammation. Neurons, astrocytes, and microglia derived from embryonic and perinatal rat cortical tissue were combined in a three-dimensional hydrogel utilizing a method that facilitated cell maturation and viability. Chemical challenge of the cultures with a broad pro-inflammatory stimulus resulted in the production of inflammatory cytokines and other associated molecules commensurate with the response observed in vivo and in other in vitro systems. It was hypothesized that mechanical deformation of the multitypic neural cell cultures would produce a similar response and thus validate the system as an in vitro model of traumatic brain injury-induced neuroinflammation. Mechanical injury delivered using custom-manufactured culture chambers and injury devices successfully imparted a moderate level of cell death to the cultures. It was determined that a mechanically-induced inflammatory response required chemical stimulation prior to the injury. The research presented here describes the generation and characterization of a novel in vitro culture system and its implementation in experiments designed to model secondary injury mechanisms associated with injury-induced neuroinflammation. The findings of these studies, applications of the culture system, and future research avenues are discussed.

BACKGROUND/AIMS: Inconsistency in the use of secondary brain injury prevention guidelines among US trauma centers after severe traumatic brain injury is prevalent in many literature sources. However, this phenomenon has not been thoroughly studied. The purpose of this DNP project is to identify the key barriers and challenges in compliance to the evidence-based guidelines for secondary brain injury prevention. DESIGN: An exploratory, emergent design was used to collect descriptive qualitative data through the use of a survey. SETTING: Six Phoenix Metropolitan Level 1 trauma centers. PARTICIPANTS: All survey participants who consented to survey completion, which had greater than six months of experience and directly worked with patients suffering from a severe TBI in the clinical setting. MEASUREMENTS: Participant demographics (work experience, area of work, job title), current awareness and use of Brain Trauma Foundation guidelines, and time duration for evidence based order set implementation. Narrative responses were also used to identify barriers to current use of the BTF guidelines and factors that may promote their use in the future. RESULTS: A total of 43 participants consented to the survey study, with completion by 35 participants. RNs (n=27), Physicians (n=2), NPs or PAs (n=5), with an average work experience of 6 to 14 years (42.86%). A total of n=22 (62%) of participants were unaware of the current BTF guidelines for severe TBI and only 25% (n=9) aware that their facility has a protocol based on the BTF guidelines for severe TBI, while 51% (n=18) were unsure if their facility had a protocol. Barriers were identified in narrative form and were consistent with awareness/education, provider congruence, communication, and order set/protocol process improvement. CONCLUSION: The understanding of current patient management for severe TBI based on the BTF guidelines is sporadic among the greater Phoenix area Level 1 trauma centers. Requiring proof of BTF guidelines compliance by the ACS at time of Level 1 certification may increase the consistent recommended use of the BTF guidelines for the care of severe TBIs.

The scientific problem of the study Brain concussion is the most common subtype of the post-concussion syndrome in childhood. This is a mild traumatic brain injury that accounts for 80-90℅ of all cases. Individuals who have sustained brain concussion, i.e. mild traumatic brain injury, frequently complain of various symptoms that are commonly defined as the post-concussion syndrome. Such symptoms are headache, dizziness, nausea, attention disorders, memory problems, sleep disturbances, learning problems, fatigue, emotional instability, mood changes, anxiety, fear, etc. – all of these are defined in the International Classification of Diseases. The symptoms of the post-concussion syndrome are non-specific and subjective. Some patients indicate similar symptoms even without having experienced head injury; these symptoms can occur in the presence of other health disorders, such as the fatigue syndrome, neurasthenia, hyperactivity and attention disorders, as well as in cases of anxiety, mood and emotional disorders, and depression. During the last 25 years, over 500 articles on mild traumatic brain injury have been published in psychological literature, and a similar number of publications in medical literature. The results of scientific studies are quite different, and the variety of the results is still inciting heated scientific debates. Some researchers insist that brain concussion has long-tern sequelae. On the other hand, an opinion has emerged that even if... [to full text]

This thesis examines the associations between substance use/ misuse and mental health outcomes among Canadians with a Traumatic Brain injury (TBI). Its primary aim is to explore whether or not individuals with a TBI have higher rates of substance use/misuse and poorer mental health than Canadians without a TBI, and to examine two competing hypothesis that help to explain these behaviours -- the impaired brain functioning and the general coping hypotheses. Drawing on data from the 2009-2010 Canadian Community Health Survey, a nationally representative cross-sectional survey, this research assessed substance use and mental health outcomes among those with a TBI, as well as two control groups: (1) individuals with a back or spinal injury; and (2) healthy non-injured controls. Analyses include descriptive statistics and multivariate regressions (logistic and multinomial) adjusting for a range of injury and socioeconomic variables. Those with a TBI demonstrated significantly elevated rates of binge drinking, illicit drug use, and having an anxiety disorder relative to non-injured Canadians, and provided partial support for both the impaired brain functioning and general coping hypotheses to substance use. These findings indicate that public health policy should increase awareness amongst healthcare and social workers on the necessity of continued follow-up of those who experience a TBI in order to reduce future health conditions and to reduce the likelihood of re-injury.