Every year an estimated 42 million people worldwide suffer a mild traumatic brain injury (MTBI) or concussion, with approximately 3.6 million sports related concussions occurring yearly in the United States alone (Bailes, 2015, Azad et al., 2015). An MTBI is an acute brain injury resulting from mechanical energy to the head from external forces (Bailes 2015). Symptoms of an MTBI include visual disturbances, dizziness, nausea and vomiting, light sensitivity, loss of balance, and a general feeling of fatigue (Bailes 2015). MTBI’s are first diagnosed through changes in ImPACT baseline scores as well as Vestibular Ocular Motor Screening (Mucha et al., 2014). Repetitive MTBI and/or repetitive sub-concussive head trauma have been tentatively linked to increased risk for a variety of neurodegenerative diseases including chronic traumatic encephalopathy (CTE) (Gardner et al., 2015). The major limitation of the link between MTBI and CTE is that CTE can only be diagnosed post-mortem (Azad et al., 2015). Due to that limitation, the prevalence of CTE is unknown and the amount of MTBI or sub-concussive trauma exposure necessary to produce CTE is unclear (Gardner et al., 2015). Newer methods of research including SNTF immunostaining and L-COSY are being further developed and studied to better diagnose MTBI and its link to CTE by exploring changes in brain protein formation and brain neurochemistry (Johnson et al., 2015, Lin et al., 2015). Through research development and case studies on professional American football players and boxers, a link between MTBI, particularly repetitive MTBI and CTE has been formed (Maroon et al., 2014).

The prevalence of injuries from improvised explosive devices (IEDs) in recent U.S. military conflicts has highlighted the lack of knowledge of the acute and long-term consequences of blast exposure. Real-world blast exposure is complex and multi-phasic. It is unclear whether the shock wave component of blast exposure (primary blast) can cause traumatic brain injury (TBI); however, other blast components, such as tertiary blast (inertial loading mechanics), have known potential to injure the brain. Clinical and in vivo studies suggest that complex blast loading of the whole body and head can result in acute and delayed behavioral deficits and neurodegeneration, yet tertiary blast exposure or injury to the body can initiate a systemic response that complicates understanding of this pathology. To set safe thresholds for primary blast exposure and design headgear that can guard against primary blast, tolerance criteria for primary blast specific to brain must be defined. We developed and validated a model of primary blast injury for use with in vitro organotypic hippocampal slice cultures (OHSCs) and determined that primary blast without concomitant tertiary blast loading or systemic response can injure isolated brain samples. This work was the first to define a cell death tolerance criterion for OHSCs to primary blast and report that the threshold for deficits in neuron function was below the threshold for cell death. Mild TBI (mTBI) or concussion, by definition, results in an altered mental state that can include loss of consciousness (LOC) for less than 30 minutes, dizziness, confusion, and retrograde amnesia. These symptoms typically subside within a week after injury; however, for some patients who experience multiple concussions over a relatively short period, these symptoms can persist for a year or longer; persistence of mTBI symptoms is called post-concussion syndrome (PCS). Studies suggest an initial mechanical trauma to the brain can initiate a period of time during which the brain is more vulnerable to additional injury. Little is known about this phenomenon; therefore the current standard of care for patients suffering from concussion is rest and removal from activities with a risk of additional brain trauma. During combat deployment, over 89% of service members reported an incidence of altered mental state and over 86% reported LOC following 2 or more exposures to blast. We evaluated the response of OHSCs to repetitive primary blast (shock wave loading) and repetitive tertiary blast (stretch injury) separately, characterizing the period of vulnerability that follows an initial insult to define safe rest-periods after blast-exposure and better understand pathologies of more complex injuries, i.e. combined primary and tertiary blast. Long-term potentiation (LTP) was significantly reduced by 2 primary blast exposures delivered 24 hours apart. An initial shock wave exposure increased tissue vulnerability to subsequent exposure, which lasted as long as 72 hours but not longer than 144 hours. Repetitive primary blast exposure also increased microglial activation. Similarly, a single mild stretch injury initiated a period of heightened vulnerability to subsequent mild stretch that lasted at least 72 hours but not longer than 144 hours long. Repetitive stretch injury significantly increased cell death, nitrite concentration, and astrogliosis and significantly reduced LTP. We also tested delayed administration of memantine as a treatment for repetitive stretch injury. Memantine is approved by the Food & Drug Administration for the treatment of Alzheimer’s disease, and preclinical studies suggest memantine may be neuroprotective following TBI. Cell death was reduced and LTP was rescued by delayed memantine treatment. Along with further preclinical and clinical investigation of repetitive primary and tertiary blast exposure, these studies may aid in setting safe rest periods and identifying new therapies for service members exposed to blast. This research has shown that primary and tertiary blast exposure can injure OHSCs causing cell death, altering neuron function, and increase vulnerability to a subsequent exposure. These studies expand our understanding of the neuropathology of primary and tertiary blast loading and evaluate methods to improve outcome after repetitive injuries with complementary strategies including rest periods and drug-treatment.

A concussion can result in a wide range of signs and symptoms including physical, cognitive, emotional and sleep-related symptoms. While a concussion can occur at any age, children and adolescents are at an increased risk of experiencing a concussion. Important physical consequences of concussion are balance deficits which affect approximately one in three cases. Balance is essential to perform many postures and activities and therefore it is important to accurately identify these deficits at the time of injury and during the recovery process in order to avoid potential further injury. A review of the literature regarding the different clinical and laboratory measures used to assess balance following a concussion was completed and identified several gaps in the literature. The four studies in this thesis were tailored to address these gaps in knowledge. The first study addressed the sensitivity of a gold standard clinical measure and laboratory measures of standing balance in terms of identifying balance deficits in adolescents at 1-month post-concussion. Performance on the Balance Error Scoring System (BESS) and COP measures from single and dual-task balance conditions were compared between a group of adolescents at one-month post-concussion and a group of non-injured adolescents. The results demonstrated that COP measures from single and dual-task conditions identified balance deficits in the concussed group that were not captured by the BESS. The second study addressed whether self-reported balance problems are a suitable alternative to COP measures to identify balance deficits in concussed adolescents. A secondary analysis of the data from study 1 was conducted to compare COP measures from the single and dual-task conditions between concussed adolescents self-reporting balance problems, concussed adolescents self-reporting no balance problems and a group of non-injured adolescents. The results from this analysis showed that the concussed adolescents demonstrated balance deficits regardless of whether they self-reported balance problems. There is significant clinical interest that lies in the ability to predict which adolescents presenting in the emergency department with concussion will be affected with ongoing balance deficits. The third study addressed the predictive ability of a set of COP variables recorded within the first 10 days following injury in a group of concussed adolescents to predict balance performance on a dual-task condition at one-month post-injury. Seven COP variables were identified as significant predictors. A secondary objective of this study was to compare performance on the COP measures between the concussed adolescents and a group of non-injured adolescents during the first session within the first 10 days following injury and during the second session at one-month post-injury and to compare performance between sessions within each group. The between session comparisons showed that performance remained relatively stable across sessions within both groups. In contrast, the between group comparisons revealed several significant differences in COP measures between the concussed and non-injured groups. The fourth study in this thesis addressed the association between balance and saccadic eye movements in concussed adolescents. Impaired saccadic eye movements are an important consequence of concussion and may be associated with balance deficits since both processes are dependent on several of the same cortical structures and brainstem areas. In this study, concussed and non-injured adolescents performed three different dual-task balance conditions involving either a high cognitive load, a low cognitive load and a gaze shifting component or a high cognitive load and a gaze shifting component. The results demonstrated that the concussed adolescents swayed over larger 95% ellipse areas while performing the two dual-tasks with the gaze shifting component, but these larger amounts of sway were not associated with an increase in saccades. Taken together, these four studies extend the current knowledge regarding balance performance in concussed adolescents and provide results that can be applied to balance assessments for concussion.

Postmortem brains from young athletes with a history of repetitive concussive head injury and military service personnel with history of blast neurotrauma revealed evidence of parenchymal contusion, myelinated axonopathy, microvasculopathy, neuroinflammation, neurodegeneration, and phosphorylated tauopathy consistent with chronic traumatic encephalopathy (CTE) (L. E. Goldstein et al., 2012). The mechanisms by which head trauma induces acute concussion and chronic sequelae are unknown. To elucidate the mechanistic connection between traumatic brain injury (TBI), acute concussion and chronic sequelae, including CTE, require the use of animal models. This doctoral dissertation investigated the hypothesis that closed-head impact injury in mice triggers acute neurological signs associated with sport-related concussion as well as brain pathologies and functional sequelae associated with CTE. To test this hypothesis, we developed a mouse model of impact neurotrauma that utilizes a momentum transfer device to induce non-skull deforming head acceleration, triggering transient neurological signs consistent with acute concussion and traumatic brain injury (TBI) in unanesthetized C57BL/6 mice. The Boston University Concussion Scale (BUCS) was developed to assess neurological signs that are consistent with acute concussion in humans. Mice exhibited contralateral circling and limb weakness, locomotor abnormalities, and impaired gait and balance that recapitulate acute concussion in humans. Concussed mice recovered neurological function within three hours, but demonstrated persistent myelinated axonopathy, microvasculopathy, neuroinflammation, and phosphorylated tauopathy consistent with early CTE. Concussive impact injury also induced blood-brain barrier disruption, neuroinflammation (including infiltration peripheral monocytes and activation microglia), impaired hippocampal axonal conduction, and defective long-term potentiation (LTP) of synaptic transmission in medial prefrontal cortex. Kinematic analysis during impact injury revealed head acceleration of sufficient intensity to induce acute concussion, traumatic brain injury (TBI), early CTE-linked pathology, and related chronic sequelae. Surprisingly, the presence or degree of concussion measured by BUCS did not correlate with brain injury. Moreover, concussion was observed following impact injury but not blast exposure under conditions that induce comparable head kinematics. Empirical pressure measurements and dynamic modeling revealed greater pressure on the head and compression wave loading in the brain during impact compared to blast neurotrauma. These findings suggest acute concussion is triggered by focal loading of energy that transit the brain before onset of macroscopic head motion. By contrast, the forces associated with rapid head motion is sufficient to induce CTE-linked pathology. Our results indicate that while acute concussion and chronic sequelae may be triggered by the same insult, the pathophysiological responses underpinning these effects are engaged through distinct mechanisms and time domains. Our results indicate that concussion is neither necessary nor sufficient to induce acute brain injury or chronic sequelae, including CTE. / 2018-02-17T00:00:00Z

Experiences of Youth Recreation Sport Organizations' Administrators with Implementation of Maryland Concussion Law by Donelle Damali Ainsworth-McKenna MHSA, The George Washington University, 2004 BS, Morgan State University, 2000 Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Health Services Walden University September 2015 There have been statewide concussion policies implemented in all 50 states and the District of Columbia to address the problem of sports-related concussions in youth athletes. The efforts to implement the requirements of these laws have mainly focused on high school athletics, despite evidence that pre-high school youth athletes who participate in organized community sports through recreation sport organizations are sustaining concussions at a similar rate as high school athletes. Thus, this study explored the implementation of the Maryland concussion law in youth sports recreation organizations in Laurel, Maryland that serve pre-high school youth athletes aged 5-14 years. A qualitative approach was utilized to conduct this study. Administrators of such youth sports and recreation organizations were interviewed to answer the central research question about how the Maryland concussion law is being implemented in youth sport recreation organizations in the state. The diffusion of innovations theory was the theoretical framework used to guide this study as well as to explore barriers to and facilitators of implementing this policy. NVivo software was used to analyze the data, and the results identified concussion training, guidelines, resources, and policing as integral to implementation of the policy. These findings can be used to inform policies, implementation, and best practices for this policy. Thus the individual and community implications for positive social change include behavior change to prevent, identify, and manage concussions in youth athletes to reduce the potential impact of concussions in youth athletes.

Graduation date: 2006

The aim of the study: by historical and prospective cohort studies to investigate the validity of postconcussion syndrome as a useful clinical entity in adults. The objectives of the study: 1. To determine the prevalence and degree of headache, dizziness and cognitive dysfunction as well as headache diagnoses after concussion and in controls with minor non-head injuries 2-3 years after the trauma and to make a comparison of these symptoms in both groups. 2. To evaluate the degree of all other symptoms attributed to the postconcussion syndrome 2-3 years after concussion and to compare it with the degree of the same symptoms experienced by controls. 3. To determine the prevalence and duration of acute posttraumatic headache. 4. To determine the prevalence and degree of symptoms of the postconcussion syndrome after concussion and in controls 3 months and 1 year after the trauma and to make a comparison of these symptoms in both groups. 5. To compare the severity of symptoms 1 year after the trauma between concussion patients and controls in relation to marital status and education. 6. To evaluate the influence of duration of unconsciousness and anterograde amnesia on the severity of headache and cognitive dysfunction. The present study was unable to confirm the concept of the postconcussion syndrome as a useful diagnostic entity. The postconcussion syndrome has therefore little validity.

Traumatic brain injury (TBI) is a major cause of death and disability throughout the world with few pharmacological treatments available for individuals who suffer from neurological morbidities associated with TBI. Cellular and molecular pathological processes initiated at the time of injury develop into neurological impairments, with chronic sleep disorders (insomnia, hypersomnolence) being among the somatic, cognitive and emotional neurological impairments. Immediately post-injury, TBI patients report excessive daytime sleepiness, however, discordant opinions suggest that individuals should not be allowed to sleep or should be frequently awoken following brain injury. To provide adequate medical care, it is imperative to understand the role of acute post-traumatic sleep on the recovery of neurological function after TBI. The aim of this thesis was to examine post-traumatic sleep after experimental TBI, defined as an increase in sleep during the first hours post-injury. In these studies, we non-invasively measured sleep activity following diffuse brain injury induced by midline fluid percussion injury to examine the architecture of post-traumatic sleep in mice. We detected significant injury-induced increases in acute sleep for six hours regardless of injury severity or time of day injury occurred. We found concurrent increases in cortical levels of the sleep promoting inflammatory cytokine interleukin 1-beta. We extended the timeline of post-injury sleep recording and found increases in post-traumatic sleep are distinctly acute with no changes in chronic sleep following diffuse TBI. Further, we investigated if post-traumatic sleep was beneficial to neurological outcome after brain-injury by disrupting post-traumatic sleep. Disruption of post-traumatic sleep did not worsen functional outcome (neuromotor, sensorimotor, cognition) at one week after diffuse TBI. With sufferers of TBI not always seeking medical attention, our final studies investigated over-the-counter analgesics and their effect on post-traumatic sleep and functional outcome. Acute administration of analgesics with varying anti-inflammatory properties had little effect on post-traumatic sleep and functional outcome. Overall, these studies demonstrated translational potential and suggest sleep after a concussion is part of the natural recovery from injury. While disrupting sleep does not worsen outcome, it is in no way beneficial to recovery. Additionally, a single analgesic dose for pain management following concussion plays little role in short term outcome.

Many athletes and spectators believe that experiencing and controlling psychological momentum is a critical component to achieving success in sport (Perreault, Vallerand, Montgomery, & Provencher, 1998; Stanimirovic & Hanrahan, 2004). Despite this, little is known regarding why some individuals perceive momentum differently than others. This study was designed to determine if optimistic thinking has a relationship with psychological momentum perceptions. Female Division I NCAA volleyball players (N = 68) completed the Life Orientation Test – Revised (Scheier, Carver, & Bridges, 1994), the Sport Attributional Style Scale - Short (Hanrahan & Grove, 1990b), and a psychological momentum survey. The results indicated that attributional style constructs intentionality and globality were significant predictors of psychological momentum perceptions. Also, participants had greater disagreement regarding the momentum value of early and late points in a set than those in between. Neither dispositional optimism nor sport-specific optimistic attributional style were correlated with psychological momentum perceptions. Future attempts to measure psychological momentum perceptions should consider a mixed methods approach along with more ecologically valid assessment protocols. / Department of Psychological Science

Concussions are injuries that can result in debilitating symptoms, suffered by people of all ages, with children being at elevated risk for injury. Falls account for over 20% of head injuries worldwide, and up to 50% of concussive injuries in children. Following a concussion, children typically take longer for symptoms to resolve compared to adults. It is unknown whether or not children are more, less, or equally susceptible to concussive injury based on the mechanical response, with researchers divided on the subject. There is currently a paucity of published data for concussive injuries in children, with few studies investigating impact biomechanics and strain response in the brain using FE models. Those that exist typically rely on scaled adult models that do not capture age-dependent geometric properties, material properties of tissues, and the developmental stage of the brain reflected by the patterns of grey and white matter within the brain. Newer child models are being developed, however at present they are focused on car crash investigations that do not offer an accurate reflection of sports-related impacts, and those that could be experienced from day-to-day activities since impact characteristics (e.g. magnitude, duration, surface compliance) differ largely between these types of events. Strain magnitudes differ between events causing concussion in adults (falls, collisions, punches, and projectiles), so it follows that the unique impact characteristics of car crash events do not typically coincide with those associated with sports impacts. Car crash events can result in much longer impact durations compared to sporting impacts (100 ms duration in car crashes vs. 5-30 ms in sports impacts). The purpose of this thesis was to assess how the mechanical response of the brain in young children near 6 years old differs from an adult brain in cases resulting in concussive injury for sports impacts. Study one created a novel FE model of a 6-year-old brain, using medical images to extract an accurate representation of the geometry and tissues inside the head of a 6-year-old child. The developmental stage of the younger brain was captured using a highly-refined mesh to accurately represent the folds of white matter within the cerebrum. With no intracranial data for child cadavers available, published data of adult cadavers was used to validate the brain motion from impacts. Comparisons were made to a scaled adult model to highlight how the different model constructions influence brain motion and resulting strains. The new model showed higher correlation to the cadaver data compared to the scaled model, and yielded “good biofidelity” measures when assessed using a modified version of the normalized integral square error method. For young children, the new model was proposed to be more appropriate for concussion investigations as it captures age-appropriate geometry, material properties, and developmental stage of the brain, reflected in the patterns and volumes of grey and white matter within the brain. Study two tested the model for sensitivity across three levels of surface compliance and impact velocity consistent with sport impact events, and compared strain responses to a scaled adult model. The 6-year-old model showed unique strain responses compared to the scaled adult model with peak strains being lower across most impact events. Strain patterns also differed between models, with less strain being transmitted into the white matter in the 6-year-old model. Low compliance impacts yielded highest differences in strains (~30%), moderate compliance impacts yielded more similar strains (~9% lower), with high compliance impacts showing a location dependent response with frontal impacts being 14% lower, and side impacts being 9% higher than the scaled model. The sensitivity study characterized the model responses, allowing for better comparisons between the two different model constructions. Study three then compared the strain responses of reconstructed real-world concussive events for both children and adults. Forty cases of concussion from falls in children and adults (20 children aged 5-7, 20 adults) were reconstructed using physical models, with the measured impact kinematics used to load the FE models. Concussive cases of children showed lower strains than adults, finding a velocity driven relationship since the child concussions occurred at lower impact velocities compared to the adults. Lower peak strains, as well as cumulative strains in the child cases suggest that children are vulnerable to concussion at lower strain compared to adults. Protective strategies for children should address this vulnerability, no longer relying on product scaling to create head protection for youth.