Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head trauma and mild traumatic brain injuries (mTBIs) and has been associated with contact sports such as football, boxing, and ice hockey. CTE is a slowly progressing neurological disease that is often clinically associated with symptoms of memory loss, decline in cognitive function, behavioral changes such as increased impulsivity and aggression, and/or suicidal thoughts. Advanced stages of the disease present with more severe neurological changes such as dementia, speech and gait abnormalities, and parkinsonism. Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig Disease) is a progressive and fatal neurodegenerative disease characterized by motor neuron loss and corticospinal tract degeneration. While 90-95% of ALS cases are sporadic in nature, many genetic mutations have been identified that contribute to familial forms of the disease. The etiology of sporadic ALS is unknown but it is likely caused by a complex interaction of various genetic and environmental risk factors. Epidemiological evidence suggests that one such risk factor is brain trauma, the main risk factor associated with the development of CTE. In this study the spinal cord tissue of twelve athletes diagnosed with CTE who also developed a progressive motor neuron disease and showed symptoms of profound muscle weakness, atrophy, spasticity, and fasciculations several years before death was examined. The spinal cord tissue from these 12 CTE cases with motor neuron disease (CTE+MND) was compared to the spinal cord tissue of 10 sporadic ALS control cases. Results showed a difference in frequency of tau pathology between the two disease cohorts, as one-third of CTE+MND cases and none of the ALS cases showed tau immunoreactivity. In addition, TDP-43 immunoreactivity was present in every CTE+MND case but one and was present in all ALS cases. Motor neuron inclusions were positive for both FUS and p62 in both cohorts, and no distinct differences were observed cystatin C pathology. Overall, this suggests that the spinal cord inclusions in CTE+MND have a similar composition to sporadic ALS. However, there is an increased frequency of tau pathology in CTE+MND though this result did not reach statistical significance in this study.

It has been postulated that there could be a connection between traumatic brain injury (TBI) and motor neuron disease (MND), including amyotrophic lateral sclerosis (ALS). As chronic traumatic encephalopathy (CTE) is caused by repeated TBI and is a newly examined disease, there has been little evaluation of the potential relationship between CTE and ALS. It was proposed that CTE is a risk factor for not only MND, but also ALS. There is significant evidence that even a single TBI is a risk factor for Parkinson's disease (PD), thought to be invoked by the inflammatory process that the brain undergoes following a TBI. General rigorous physical activity with trauma to the trunk or extremities does not appear to be a risk factor for ALS. However, physical activity with associated head traumas, especially repeated head traumas, does seem to increase the likelihood of developing ALS. The biological mechanism for this is suspected to be increase in free radicals during exercise in individuals who are predisposed to decreased antioxidant function. Additionally, individuals who have suffered repeated head trauma, even amongst the general population in a non-athletic setting, has been shown to drastically increase the individual's chance of developing ALS. CTE, which is most common in athletes, is speculated to be caused by TAR DNA-binding protein 43 (TDP-43), tau neurofibrillary tangle (NFT), and beta-amyloid (A-Beta) protein inclusions in brain tissue following a multitude of TBI during high level sport activity. There are individuals who suffer initially CTE, followed by ALS, indicating CTE is clearly a risk factor for ALS. Anatomically, the TDP-43, NTF, and A-Beta; inclusions are present in the brain tissue of both individuals with CTE alone as well as the individuals with CTE and ALS. The anatomic difference between these two pathologies is the inclusion of these three proteins in the spinal cord of ALS patients as well. Unfortunately, there are indications that previous studies of professional athletes and their development of ALS have presented with significant issues including confounding factors of the subpopulation and sample sizing. Additionally, the anatomical cause of TBI leading to ALS is still unknown. Further evaluation on the relationship between head injury and ALS must be dedicated to investigating the mechanism involved in developed PD versus ALS following TBI. The biologic sequence following TBI that leads to ALS must be examined and compared to individuals whom develop ALS but did not suffer TBI. Moreover, an assessment must be made to determine what causes some individuals to develop protein inclusions solely in the brain tissue, leading to CTE, and some individuals to have an advancement of the protein inclusions into the spinal cord, leading additionally to CTE followed by ALS.

Chronic Traumatic Encephalopathy (CTE) has been linked to contact sports, most notably boxing and American football, due to their propensity for repetitive head impacts. Concerns in the community for the safety of athletes in all contact sports has driven a significant amount of research into concussions, their long term effects, and strategies for treatment and prevention. Knowledge of long term brain health in response to neurotrauma is limited, a gap especially noticeable in the literature on non-catastrophic brain injuries sustained as a child. Concussion is a common injury that is often self-resolving with no lasting neurologic or cognitive deficits. Although repetitive brain trauma is hypothesized to be necessary and sufficient to lead to CTE, no human or animal models have definitively demonstrated the pathophysiologic connection or confirmed the mechanism of symptoms. The research to date has been case based, lacking prospective cohorts, with data complicated by convenience sampling. These factors limit the generalizability of conclusions. CTE is neuropathologically defined with variable symptoms; however, it is only diagnosable at postmortem autopsy making the etiology and prevalence difficult to understand. As more research is published to understand if there is an association between a neurocognitive degenerative disease and contact sports, the concentration is on professional athletes. Yet professional athletes do not represent the overwhelming majority of all contact sport participants. The proposed study will compare adults who participated in youth football, but not beyond the high school level, to a control group of adults who did not play contact sports. Evaluating their cognitive function with an online assessment, the Behavior Rating Inventory of Executive Function – Adult Version (BRIEF-A), data will be analyzed for signs of clinical cognitive impairment. The objective is to measure adults who represent the high percentage of youth football players who do not continue to the advanced levels. Data obtained from this study will help communities make informed decisions, and create the foundation for future studies on long term benefits and risks of contact sports for children.

A participação de marcadores bioquímicos na avaliação de quadros de asfixia neonatal é cada vez mais relevante. A proteína S100B tem um papel destacado nestas pesquisas. O objetivo deste estudo foi procurar destacar a importância da proteína S100B na avaliação de recém-nascidos a termo com quadros de encefalopatia hipóxico-isquêmica, assim como correlacionar com outras substâncias que também participam do processo isquêmico. Foram analisados 21 casos de recém-nascidos a termo que desenvolveram quadro de encefalopatia hipóxico-isquêmica, no período de setembro de 2003 a outubro de 2004. Realizadas coletas no 1º e 4º dia de vida e dosadas, por método imunocitoquímico, a proteína S100B e o lactato. Foi possível detectar uma correlação positiva entre as 2 substâncias, assim como, quando comparadas entre si, observou-se também significância estatística. / Biochemical markers have played an increasingly relevant role in the assessment of neonatal asphyxia. The S100B protein is particularly important in research conducted in this field. The purpose of this study was to underline the importance of S100B protein in the assessment of term newborn infants with hypoxic ischemic encephalopathy, as well as to relate it to other substances also involved in the ischemic process. An assessment was made from September 2003 to October 2004 of twenty-one term newborn infants who developed hypoxic ischemic encephalopathy. Samples were collected on the 1st and 4th day of life and S100B protein and lactate levels were calculated using the immune cytochemical method. A positive relationship was found between the 2 substances. Additionally, a comparison between the two substances showed a statistically significant correlation.

A participação de marcadores bioquímicos na avaliação de quadros de asfixia neonatal é cada vez mais relevante. A proteína S100B tem um papel destacado nestas pesquisas. O objetivo deste estudo foi procurar destacar a importância da proteína S100B na avaliação de recém-nascidos a termo com quadros de encefalopatia hipóxico-isquêmica, assim como correlacionar com outras substâncias que também participam do processo isquêmico. Foram analisados 21 casos de recém-nascidos a termo que desenvolveram quadro de encefalopatia hipóxico-isquêmica, no período de setembro de 2003 a outubro de 2004. Realizadas coletas no 1º e 4º dia de vida e dosadas, por método imunocitoquímico, a proteína S100B e o lactato. Foi possível detectar uma correlação positiva entre as 2 substâncias, assim como, quando comparadas entre si, observou-se também significância estatística. / Biochemical markers have played an increasingly relevant role in the assessment of neonatal asphyxia. The S100B protein is particularly important in research conducted in this field. The purpose of this study was to underline the importance of S100B protein in the assessment of term newborn infants with hypoxic ischemic encephalopathy, as well as to relate it to other substances also involved in the ischemic process. An assessment was made from September 2003 to October 2004 of twenty-one term newborn infants who developed hypoxic ischemic encephalopathy. Samples were collected on the 1st and 4th day of life and S100B protein and lactate levels were calculated using the immune cytochemical method. A positive relationship was found between the 2 substances. Additionally, a comparison between the two substances showed a statistically significant correlation.

A participação de marcadores bioquímicos na avaliação de quadros de asfixia neonatal é cada vez mais relevante. A proteína S100B tem um papel destacado nestas pesquisas. O objetivo deste estudo foi procurar destacar a importância da proteína S100B na avaliação de recém-nascidos a termo com quadros de encefalopatia hipóxico-isquêmica, assim como correlacionar com outras substâncias que também participam do processo isquêmico. Foram analisados 21 casos de recém-nascidos a termo que desenvolveram quadro de encefalopatia hipóxico-isquêmica, no período de setembro de 2003 a outubro de 2004. Realizadas coletas no 1º e 4º dia de vida e dosadas, por método imunocitoquímico, a proteína S100B e o lactato. Foi possível detectar uma correlação positiva entre as 2 substâncias, assim como, quando comparadas entre si, observou-se também significância estatística. / Biochemical markers have played an increasingly relevant role in the assessment of neonatal asphyxia. The S100B protein is particularly important in research conducted in this field. The purpose of this study was to underline the importance of S100B protein in the assessment of term newborn infants with hypoxic ischemic encephalopathy, as well as to relate it to other substances also involved in the ischemic process. An assessment was made from September 2003 to October 2004 of twenty-one term newborn infants who developed hypoxic ischemic encephalopathy. Samples were collected on the 1st and 4th day of life and S100B protein and lactate levels were calculated using the immune cytochemical method. A positive relationship was found between the 2 substances. Additionally, a comparison between the two substances showed a statistically significant correlation.

O presente trabalho objetivou explorar a eventual variação da expressão do mRNA e da proteína S100b no hipocampo, cerebelo e córtex cerebral de ratos neonatos em condições de anóxia, comparativamente à condições controle. Este estudo foi desenvolvido em ratos albinos, divididos em dois grupos: o grupo Experimental Anóxia (EA) e o grupo Experimental Controle (EC), que por sua vez foram subdivididos em tempos de 2, 4, 6, 12 e 24 horas no que se refere à coleta de amostras após a aplicação dos estímulos pré-estabelecidos para cada grupo. Dos períodos avaliados, nossos resultados indicaram que a anóxia proporcionou um pico na expressão gênica de S100b após duas horas e proteica após 4 horas nas áreas do hipocampo e cerebelo. O córtex cerebral do grupo EA quando comparado ao grupo EC, não apresentou nenhum aumento significante de S100b nos períodos avaliados. Os resultados obtidos contribuem de forma crucial para elucidação do papel da proteína S100b como biomarcadora na EHI, bem como no esclarecimento parcial da função deste gene com relação à fisiopatologia da doença. / The aim of the present study was to investigate the temporal variation in the expression of S100b mRNA and protein in the hippocampus, cerebellum, and cerebral cortex of newborn rats under conditions of anoxia compared with control rats. The study was performed using two groups albino rats: Experimental Anoxia (EA) and Experimental Control (EC). The animals in both EA and EC were distributed in the following subgroups relative to the time elapsed since the application of the stimuli predefined for each group: two, four, six, 12, and 24 hours. Anoxia induced a peak in the S100b gene expression after two hours and protein expression after 4 hours in the hippocampus and cerebellum. With respect to the cerebral cortex, S100b never exhibited a significant increase in the EA group compared with the EC group. The results of the present study represent a crucial contribution to the elucidation of the role protein S100b plays as a biomarker in HIE, as well as a contribution to the elucidation of the role the corresponding gene plays in the physiopathology of the disease.

Contact and collision sports (CCS) expose athletes to countless repetitive head impacts (RHI) across a single season, potentially leading to increased risk of long-term difficulties in cognition and the development of neurodegenerative disease. There is mixed literature on whether RHI from CCS result in changes to white matter and long-term neurobehavioral outcomes, therefore this research project seeks to provide supporting evidence by comparing the total volume of fluid-attenuated inversion recovery (FLAIR) white matter lesions in individuals with a history of RHI from CCS to those without a history of RHI from the Boston University Alzheimer’s Disease Research Center (BU ADRC). The RHI participants were matched to a group of non-RHI participants based on age (+/- 5 years). Effects of RHI on white matter hyperintensities (WMHs) are evaluated, while considering hippocampal volume across RHI and non-RHI groups. When controlling for age, sex, education, and total hippocampal volume, those with a history of football were found to have a significantly greater WMH volume (p=.02) compared to those without a history of football play. Compared to the non-RHI group, the RHI group including all athletes (n=42) had a greater WMH volume, although it did not reach a level of significance (p=.91). This investigation provided preliminary evidence for a link between high RHI exposure and WMHs in football players, and a non-significant relationship between RHI and increased WMHs in those with a history of CCS compared to individuals in the non-RHI group. Future research should expand upon this investigation, by examining RHI exposure and WMH consequences in a diverse assortment of sports, follow athletes longitudinally for repeated in vivo MRIs and post-mortem neuropathological confirmation, and include more female athletes.

Epilepsy affects approximately 0,5-1% of children. Epileptic seizures originate in and propagate along certain neural pathways involved in physiological processes of cognition. Consequently, cognitive impairment frequently accompanies epilepsy in childhood and contributes to diminished quality of life of these patients.The main goal of this PhD thesis was to study multiple aspects of cognitive impairment in children suffering from intractable focal epilepsy. In the first and primary study, we described for the first time the negative impact of quasi- periodic epileptiform discharges in sleep (termed "hurdles" in our work) on cognitive functions in children with focal structural epilepsy. We have also shown that epileptiform activity in sleep has a more prominent negative impact on cognitive functions than epileptiform activity in wake. Although "hurdles" are by definition generalized, they do not predict worse outcomes of epilepsy surgery, compared to controls. In the second study, we analyzed the relationship between the extent of epileptogenic zone, functional brain plasticity (evaluated by fMRI) and cognitive dysfunction in children with drug resistant temporal epilepsy. Comparing patients with isolated focal cortical dysplasia (FCD) and patients with combined pathology (FCD and hippocampal...

Background: South Africa aims to end all preventable deaths of children under the age of five as part of their commitment to the Sustainable Development Goals. More than half of these mortalities occur in the neonatal period with perinatal asphyxia as one of the leading causes. This study investigated and identified the characteristics of perinatal asphyxia and its contributing factors at a district hospital in Cape Town. Methods: A retrospective descriptive case series was performed and included all suspected cases of perinatal asphyxia referred from Mitchells Plain District Hospital (MPH)) to a specialised centre in the years 2016-2018. A data collection tool was used to extract information. Data was processed with SPSS to produce descriptive statistics and to investigate associations between variables using the Chi-square tests. Results: The study included 29 cases of suspected perinatal asphyxia. Ten (34.5%) had abnormal amplitude Electroencephalograms (aEEG's) indicative of Hypoxic Ischaemic Encephalopathy (HIE) and four (13.8%) demised before day seven of life. Non-operative deliveries (p=0.005), lack of a doctor at the time of delivery (p=0.004) and neonatal chest compressions (p=0.044) were associated with abnormal aEEG's. Babies with Thompson score of equal to or more than 12 (p=0.006), neonatal seizures (p=0.036) and delayed arrival at referral hospital (p=0.005) were associated with abnormal aEEG findings. Mortality was associated with Thompson score ≥12 (p=0.007) and the need for neonatal intubation at delivery (p=0.016). Conclusions: Significant reversable factors were identified in the peri-and postpartum periods. More capacitated staff would have the greatest impact on outcomes. The profile of HIE is exceedingly complex and challenges the resources and services of district level of care. Therefore, these factors should be targeted for future development and investment to improve outcomes from district hospitals.