Mild Traumatic Brain injury (mTBI) is one of the most common forms of acquired neurological damage. However, the term 'mild' TBI is misleading because the physical, cognitive and emotional impairments that can follow from mTBI can be significant. In order to provide objective, prognostic measures for diagnosing the severity of mTBI and identifying individuals who may be at risk for poor outcomes a battery of neuropsychological measures for detecting cognitive impairment was evaluated. The Rapid Screen of Concussion (RSC) is a collection of tests assessing verbal recall, orientation, processing speed and speed of language comprehension. Previous studies have demonstrated that the RSC has acceptable reliability, validity and sensitivity to cognitive impairment that arises during the acute stages of injury. However, no studies have investigated the predictive validity of this instrument. Moreover it is unclear what additional patient or post injury variables could assist in identifying those individuals who may be at risk of poor neuropsychological outcomes following mTBI. These were among the main issues that were addressed across the five empirical studies in this thesis. A pragmatic, prospective, longitudinal and cross-sectional study of the sequelae of mTBI in patients presenting to the Department of Emergency Medicine of the Royal Brisbane and Women's hospital was the basis of this project. The first empirical chapter (chapter 2), examined the psychometric properties of two measures of verbal learning and memory and investigated their potential for discriminating between mTBI and orthopaedic controls. The performance of 93 patients with mTBI and 68 participants with orthopaedic injuries was analysed to identify the number of individuals who performed at ceiling on the Hopkins Verbal Learning test (HVLT-R) versus a 5-word test of immediate and delayed recall. While both of these verbal recall measures were effective in separating the mTBI and orthopaedic groups, overall, the HVLT-R was shown to be a more suitable measure for screening for deficits in verbal learning and memory after mTBI. Given the superiority of the HVLT-R as a measure of verbal learning and memory, chapter 3 aimed to examine whether inclusion of this test could improve the sensitivity of the RSC in mTBI compared to orthopaedic and uninjured control samples. Results were generally within the direction predicted. Significant differences were found between groups on the majority of cognitive indices assessed. Both the orthopaedic and mTBI group performed more poorly than the uninjured group on all measures except the Hopkins delayed recognition. Additional performance decrements shown by the mTBI group compared to the orthopaedic group illustrate that factors beyond the general effects of trauma influence performance and may be related to cognitive impairment specific to sustaining mTBI. Overall it was concluded that the revised RSC is a sensitive instrument deserving investigation in assessing the more long term cognitive effects following mTBI. Chapter 4 applied this sensitive battery for investigation of group and individual recovery of neuropsychological test performance and post-concussive symptom reporting up to 3-months after mTBI. A sample of 30 mTBI participants and 30 uninjured controls were serially assessed on cognitive measures and symptom report scales immediately after injury and after 1-week, 1-month and 3-months. Symptom reporting on the Rivermead post-concussive inventory separated the mTBI and control groups after 1-week but diagnostic accuracy was no greater than chance at 1 and 3-months. In contrast the mTBI group performed more poorly than controls on measures on neuropsychological measures acutely, at 1-week and 1-month, with group differences still evident after 3-months. Nonethless, a trend of progressive recovery over time was seen in the mTBI group. In chapter 5, criteria utilising the concepts of reliable and statistically significant change were applied to the data. Overall, 73% of mTBI patients were impaired on one or more tests acutely. Significant recovery was demonstrated by 20% of mTBI participants by 3-months; however recovery remained incomplete for half of the mTBI participants by 3-months. These results highlighted the importance of an individual approach to the assessment of mTBI and support the notion that a proportion of mTBI cases may have protracted difficulties. Chapter 6 extended these findings by showing that the RSC has prognostic ability. It was found that acute neuropsychological performance on the RSC was a significant predictor of performance on an extended battery at 3-months. The final chapter provides a general discussion and synthesis of the findings. In summary, the present dissertation demonstrated that inclusion of a sensitive measure of verbal recall led to improved diagnostic validity of the RSC. Neuropsychological measures rather than symptom reporting were sensitive in detecting cognitive impairment at 3-months. Analysis of individuals showed that up to 50% of the group had failed to – demonstrate reliable recovery – that is, make improvements over and above practice effects after 3-months. Finally, acute neuropsychological performance was predictive of long term performance. Overall, the present thesis has identified a short battery of tests that is suitable for assessment of mTBI within 24 hours and may assist in identifying individuals at risk of poor cognitive outcomes after mTBI.

Mild Traumatic Brain injury (mTBI) is one of the most common forms of acquired neurological damage. However, the term 'mild' TBI is misleading because the physical, cognitive and emotional impairments that can follow from mTBI can be significant. In order to provide objective, prognostic measures for diagnosing the severity of mTBI and identifying individuals who may be at risk for poor outcomes a battery of neuropsychological measures for detecting cognitive impairment was evaluated. The Rapid Screen of Concussion (RSC) is a collection of tests assessing verbal recall, orientation, processing speed and speed of language comprehension. Previous studies have demonstrated that the RSC has acceptable reliability, validity and sensitivity to cognitive impairment that arises during the acute stages of injury. However, no studies have investigated the predictive validity of this instrument. Moreover it is unclear what additional patient or post injury variables could assist in identifying those individuals who may be at risk of poor neuropsychological outcomes following mTBI. These were among the main issues that were addressed across the five empirical studies in this thesis. A pragmatic, prospective, longitudinal and cross-sectional study of the sequelae of mTBI in patients presenting to the Department of Emergency Medicine of the Royal Brisbane and Women's hospital was the basis of this project. The first empirical chapter (chapter 2), examined the psychometric properties of two measures of verbal learning and memory and investigated their potential for discriminating between mTBI and orthopaedic controls. The performance of 93 patients with mTBI and 68 participants with orthopaedic injuries was analysed to identify the number of individuals who performed at ceiling on the Hopkins Verbal Learning test (HVLT-R) versus a 5-word test of immediate and delayed recall. While both of these verbal recall measures were effective in separating the mTBI and orthopaedic groups, overall, the HVLT-R was shown to be a more suitable measure for screening for deficits in verbal learning and memory after mTBI. Given the superiority of the HVLT-R as a measure of verbal learning and memory, chapter 3 aimed to examine whether inclusion of this test could improve the sensitivity of the RSC in mTBI compared to orthopaedic and uninjured control samples. Results were generally within the direction predicted. Significant differences were found between groups on the majority of cognitive indices assessed. Both the orthopaedic and mTBI group performed more poorly than the uninjured group on all measures except the Hopkins delayed recognition. Additional performance decrements shown by the mTBI group compared to the orthopaedic group illustrate that factors beyond the general effects of trauma influence performance and may be related to cognitive impairment specific to sustaining mTBI. Overall it was concluded that the revised RSC is a sensitive instrument deserving investigation in assessing the more long term cognitive effects following mTBI. Chapter 4 applied this sensitive battery for investigation of group and individual recovery of neuropsychological test performance and post-concussive symptom reporting up to 3-months after mTBI. A sample of 30 mTBI participants and 30 uninjured controls were serially assessed on cognitive measures and symptom report scales immediately after injury and after 1-week, 1-month and 3-months. Symptom reporting on the Rivermead post-concussive inventory separated the mTBI and control groups after 1-week but diagnostic accuracy was no greater than chance at 1 and 3-months. In contrast the mTBI group performed more poorly than controls on measures on neuropsychological measures acutely, at 1-week and 1-month, with group differences still evident after 3-months. Nonethless, a trend of progressive recovery over time was seen in the mTBI group. In chapter 5, criteria utilising the concepts of reliable and statistically significant change were applied to the data. Overall, 73% of mTBI patients were impaired on one or more tests acutely. Significant recovery was demonstrated by 20% of mTBI participants by 3-months; however recovery remained incomplete for half of the mTBI participants by 3-months. These results highlighted the importance of an individual approach to the assessment of mTBI and support the notion that a proportion of mTBI cases may have protracted difficulties. Chapter 6 extended these findings by showing that the RSC has prognostic ability. It was found that acute neuropsychological performance on the RSC was a significant predictor of performance on an extended battery at 3-months. The final chapter provides a general discussion and synthesis of the findings. In summary, the present dissertation demonstrated that inclusion of a sensitive measure of verbal recall led to improved diagnostic validity of the RSC. Neuropsychological measures rather than symptom reporting were sensitive in detecting cognitive impairment at 3-months. Analysis of individuals showed that up to 50% of the group had failed to – demonstrate reliable recovery – that is, make improvements over and above practice effects after 3-months. Finally, acute neuropsychological performance was predictive of long term performance. Overall, the present thesis has identified a short battery of tests that is suitable for assessment of mTBI within 24 hours and may assist in identifying individuals at risk of poor cognitive outcomes after mTBI.

xvi, 68 p. : ill. / Approximately 1.5 million concussions occur annually in the United States, many affecting individuals between the ages of 15 and 18. Little is known about this age group's response to a concussion as they have been thought to respond differently than adults due to immature brain development. Additionally, relying on symptoms alone to determine level of brain function may lead to early return back to sport participation. Through the use of 3 computerized tests, neuropsychological and attentional deficit recovery post concussion was assessed between 12 subjects with concussions and 12 controls up to 2 months after injury. Memory tasks and symptoms resolved within a week after injury. Executive function tests showed small group differences up to two months post injury, suggesting these types of tests may be a useful tool in the evaluation of concussion recovery and provide an objective measure in evaluation. / Committee in charge: Dr. Li-Shan Chou, Chair; Dr. Lou Osternig, Member; Dr. Sierra Dawson, Member; Dr. Grace Golden, Member

One of the consequences of traumatic brain injury is the postconcussion syndrome. The symptoms in this syndrome include headache, dizziness, poor memory, poor concentration, easy fatigue, drowsiness, irritability, sensitivity to light, sensitivity to noise, low alcohol tolerance, visual problems, auditory problems, nausea, vomiting, anxiety, and depression. Several factor analytic studies have shown that these symptoms load onto cognitive and noncognitive factors (Bohnen, Twijnstra, & Jolles, 1992). The aim of this study was to determine whether patients who report different symptoms also evidence differences in cognitive deficits, as indexed by reaction time. For this purpose 106 subjects (mean age 25.92 years; SD=6.05) of both sexes were tested on 8 reaction time tasks adapted from Shum, McFarland, Bain, and Humphreys (1990). There were 54 traumatic brain injury patients (mean age 26.40 years; SD=6.23) drawn from three Pretoria hospitals. They were heterogeneous with respect to diagnosis and severity of injury. For the controls (N=52), the mean age was 25.43 years (SD=5.88). The eight reaction time tasks constituted 4 task variables, each with 21evels. From these tasks, 36 reaction time indexes were derived. The indexes were classified into 4 groups, viz., reaction time (RT), movement time (MT), total reaction time (TT), and subtraction scores (SB, the difference between the 2 levels for each task variable). RT reflects the decision component and MT reflects the response execution component of reaction time. Partial correlation coefficients for all symptoms (p0,01) showed that some symptoms were most frequently associated with RT whilst others were most frequently associated with MT. On factor analysis with varimax rotation, symptoms loaded predominantly with SB scores. Symptoms also loaded with different task variablseuiggesting that they correlated with deficits on different stages of information processing. Taking into account possible methodological constraints that were discussed, these results confirm that different symptoms within the postconcussion syndrome correlate with different cognitive deficits. The correlations between symptoms and indices of reaction time are moderated by the characteristics of the symptoms (frequency & intensity), and the duration since injury. These findings have significance for understanding the aetiology of the postconcussion symptoms and for planning treatment. / Psychology / Ph. D. (Psychology)

Concussions are the injury and symptoms that can result from transmission of a biomechanical force to the brain. They represent a significant global health burden, and are the subject of a growing body of medical research. A concussion can only be definitively diagnosed by a medical professional based on symptoms, although advanced neuroimaging and biomarker-based approaches are promising future diagnostic tools. There is no treatment for concussion beyond following return-to-work or -play guidelines, which recommend avoiding strenuous physical and cognitive activities until they no longer exacerbate symptoms. Preclinical models of concussion have been used to examine pathophysiological processes underlying symptoms, which is an important step in developing tools for diagnosis and treatment. Historically the clinical translation of preclinical concussion research has been limited, and the use of anaesthesia, and preference for adult male rats may contribute to this. These means of reducing variability are justified, but preclinical research moving forward should address these limitations to translatability by including more clinically relevant subjects and avoiding anaesthesia. To this end, we developed a new preclinical model for pediatric concussion. Our awake closed head injury (ACHI) model is well-suited to this purpose because it produces a helmeted closed-head injury involving vertical and rotational displacement of the head, and does not require anaesthesia. Before the ACHI model can be used to investigate concussion mechanism, diagnosis, and treatment, it needs to be characterized to demonstrate that it produces clinically relevant neurobehavioral and pathological changes. We developed a modified neurologic assessment protocol to test neurologic function immediately after each injury. The Barnes maze, elevated plus maze, open field, and Rotarod were used to measure injury-related changes in cognition, anxiety, and motor function. The Barnes maze reversal task was used to detect more subtle cognitive impairments of executive function. Structural MRI was used to search for visible lesion, hemorrhage, or atrophy; and silver-stain histology was used to detect neurodegeneration. We determined repeated ACHI produced acute neurologic impairment with the NAP, and a mild spatial learning deficit potentially mediated impaired cognitive flexibility in the Barnes maze and reversal training. These were accompanied by neurodegeneration in the optic tract, hippocampus, and ipsilateral cortex during the first week of recovery. Thus, following the internationally recognised definition developed by the concussion in sport group, we demonstrated 1) an “impulsive” force transmitted to the head results in 2) the rapid onset of short-lived neurologic impairment that resolves spontaneously. This occurs 3) with normal structural neuroimaging, and 4) produces cognitive impairment, and LOC in a subset of cases. The ACHI model is the first in Canada to forego anaesthesia, and this is the first demonstration of neurocognitive impairment accompanied by diffuse neurodegeneration in the absence of structural MRI abnormalities after mild traumatic brain injury in juvenile male and female rats. / Graduate

Background: Vestibular dysfunction, characterized by nausea, dizziness, imbalance, and/or gait disturbance, represents an important sport-related concussion (SRC) subtype associated with prolonged recovery. Vestibular physical therapy promotes recovery; however, the benefit of earlier therapy is unclear. Hypothesis: Earlier vestibular therapy for young athletes with SRC is associated with earlier return to play (RTP), return to learn (RTL), and symptom resolution. Study Design: Retrospective cohort study. Level of Evidence: Level 3. Methods: Patients aged 5 to 23 years with SRC who initiated vestibular rehabilitation therapy (VRT) from January 2019 to December 2019 were included and patient records were reviewed. Therapy initiation was defined as either early, ≤30 days postinjury, or late (>30 days). Univariate comparisons between groups, Kaplan-Meier plots, and multivariate Cox proportional hazard modeling were performed. Results: Overall, 23 patients (10 early, 13 late) aged 16.14 ± 2.98 years and 43.5% were male patients. There was no difference between group demographics or medical history. Median initial total and vestibular symptom scores were comparable between groups. The late therapy group required additional time to RTP (110 days [61.3, 150.8] vs 31 days [22.5, 74.5], P = 0.03) and to achieve symptom resolution (121.5 days [71, 222.8] vs 54 days [27, 91], P = 0.02), but not to RTL (12 days [3.5, 26.5] vs 17.5 days [8, 20.75], P = 0.09). Adjusting for age and initial total symptom score, earlier therapy was protective against delayed symptom resolution (P = 0.01). Conclusion: This pilot study suggests that initiating VRT within the first 30 days after SRC is associated with earlier RTP and symptom resolution. Further prospective trials to evaluate if even earlier VRT should be pursued to further improve recovery time. Clinical Relevance: Clinicians should screen for vestibular dysfunction and consider modifying follow-up schedules after SRC to initiate VRT within a month of injury for improved outcomes.

Tradition measures of recovery, such as patient-reported symptoms, objective measures such as balance, specific dimensions such as depression, fatigue, cognitive status, and exercise tolerance do not fully capture the impact of the concussion on performing individual activities and participating in life situations as experienced by the patient. No concussion-specific measure of functional status currently exists. Objectives The overarching purpose of this dissertation was to develop a concussion-specific measure of functional status. There were two specific objectives: 1. To examine the concept of functioning post-concussion; 2. To generate questionnaire items based on a conceptual model of functioning. Methods This dissertation follows the recommendations of the Association for Medical Education in Europe as a framework with which to meet the objectives. The first objective was addressed by (1) generating a list of concussion-specific concepts through a systematic review (Chapter 3), and (2) qualitative interviews with individuals with persistent post-concussion symptoms and clinicians with concussion expertise (Chapter 4). The relationships between the concepts that emerged from those studies are presented graphically in a conceptual model to meet the second objective. The concepts were then transformed into questionnaire items and pretested through cognitive interviews with individuals with PPCS and clinicians with concussion expertise. Finally, the questionnaire items were critically evaluated for proportion of shared content against existing measures used in concussion clinical trials by coding all items to the International Classification of Functioning, Disability and Health. Results Objective 1 Three main themes emerged from the qualitative findings: (1) functioning at the level of the individual and society; (2) environmental barriers and facilitators; and (3) capacity, defined as the length of time one could perform a task before the onset of symptoms, and the length of time it took to recovery from those symptoms. Objective 2 The final questionnaire is presented as the CORE-Q, which is comprised of 53 items over three complimentary subscales, namely the Post-Concussion Functional Scale, the Concussion Modifiers Scale, and the Global Functional Recovery Scale. Each subscale corresponds to one of the three main themes. No existing outcome measure contained more than 40% of the content within the CORE-Q, or 55% of any subscale. Conclusions The CORE-Q is a unique measure of functional status post-concussion that considers functioning from a biopsychosocial perspective. Further studies are needed to assess the psychometric properties of the CORE-Q before it is adopted into clinical practice and intervention trials.

In the United States, an annual estimate of 1.36 million traumatic brain injuries present to the emergency department (ED), of which approximately 75% are concussions. Proper and timely treatment of concussion is especially important in pediatrics as children and adolescents under the age of 19 are at a higher risk for sustaining more severe and longer-lasting consequences. However, due to the wide range of symptoms at presentation, or to the potential lack of obvious symptoms, concussion can be especially difficult to diagnose in the ED setting. Neurocognitive tests provide a valuable supplement to the clinical diagnosis of concussion by objectively identifying aberrant brain activity. However, many of these tests are often too lengthy and impractical for use in the ED setting. The Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) is a 20-minute computer test that is considered to be one of the gold-standard neurocognitive tests used to diagnose concussion and track recovery. The King-Devick test (KD) is a 1-2 minute test that uses saccadic eye movements to detect suboptimal brain impairment associated with concussion. To date, there have not been any studies that analyzed the relative usability of the KD and the ImPACT in the pediatric ED (PED). The present prospective pilot study investigates the use of the KD as a neurocognitive tool for concussion assessment in the PED and at a post-ED visit, relative to the ImPACT, the gold standard tool for concussion diagnosis. We hypothesize that the change in performance in the KD will correlate with the change in the ImPACT results. To date, 20 subjects between the ages of 11-18 years old presenting to the PED within 72 hours of sustaining a head injury have completed the study. The mean age of our study population was 13.6 years. The average change in test scores between PED and follow-up were: 7.2 seconds in the KD, 0.03 points in the ImPACT reaction time, 1.8 points in verbal memory, 8.3 points in visual memory, 0.8 points in visual motor speed, and 14.9 points in post-concussion symptom scale. Analysis of the correlation of the change in the KD scores to the change in the ImPACT measures revealed that the change in the KD was significantly correlated with the change in the ImPACT reaction time (p < 0.01), and with the change in the ImPACT verbal memory (p < 0.05) in the subjects that presented with LOC, 80% of whom were male. In conclusion, our findings report that the correlation between the results of the KD and the ImPACT is more pronounced in patients presenting with more severe head trauma, such as those leading to LOC. The usability of the KD as a reliable concussion assessment tool in the PED would require further investigation with a larger sample of participants. / 2017-04-30T00:00:00Z

BACKGROUND: Sports-related head trauma has become a major public health concern with significant consequences including persistent post-concussion syndrome (pPCS) and chronic traumatic encephalopathy (CTE). pPCS is a condition where symptoms of single concussion persist years beyond the initial injury. CTE has been characterized as a condition with insidious onset following a latent period after substantial exposure to repetitive head impacts (RHI). Timing of symptom onset usually distinguishes these conditions, however in certain clinical situations a definitive diagnosis is not always clear. For these situations, a measurable distinguishing variable is necessary. LITERATURE REVIEW: Concussions are the most common form of traumatic brain injury (TBI) and are associated with a variety of neurological symptoms that usually resolve within weeks. Post-concussion syndrome (PCS) refers to cases where symptoms continue months beyond this window, and pPCS is defined as symptoms continuing over years. These conditions are temporally related single concussive events. CTE is the hallmark condition related to RHI and remains difficult to fully characterize as it currently can only be diagnosed post-mortem. Clinical features of CTE are similar to those of pPCS with notable behavioral/mood symptoms in its earliest stages, and progression to severe cognitive decline over time. Current research has shown executive dysfunction to be a common impairment among these conditions. The difference in level of dysfunction between them, if one exists, is yet to be measured. PROPOSED PROJECT: A cross-sectional analysis of executive function in four groups. A control without history of mTBI or football exposure (Non-Football – pPCS), a second control of asymptomatic subjects with football exposure (Football – pPCS), a group of pPCS patients with non-athletic mTBI history (Non-Football + pPCS), and a group of pPCS patients with football exposure (Football + pPCS). Executive functioning will be evaluated using the BRIEF-A assessment. Results will be compared to determine if significant differences in executive functioning exist between the groups. CONCLUSIONS: With previous studies showing a correlation between CTE pathological stage, worsening executive function, and increased RHI exposure, further investigation into using executive function as a distinguishing variable between early stage CTE and pPCS is warranted. SIGNIFICANCE: Results of this study, if significant, could be applied clinically to assess risk of early stage CTE in athletes with prolonged post-concussion symptoms. If results are not significant, they may still be utilized for a better understanding of the effects of isolated mTBIs and RHI on executive functioning, and provide valuable information for ongoing longitudinal studies.

Within the past few decades brain injury, or traumatic brain injury (TBI), has gained widespread attention. Early focus was on more severe forms of TBI; severity typically measured using the Glasgow Coma Scale. In more recent years, however, mild traumatic brain injury (mTBI), most notably concussions, has gained increasing interest due to the high frequency of concussions suffered in athletes of all levels and, recently, in military personnel due to blast injuries. Studies being performed have focused not only on ways to help minimize the incidence of concussion as well as treating concussive symptoms, but also on detecting concussions. Many concussions go unreported due to inadequate knowledge of concussive symptoms amongst the general population. Because many concussions go unnoticed and hence unreported the individual who has sustained a concussion is at risk for a more serious injury in the future. One such injury is Second Impact Syndrome (SIS). Second Impact Syndrome is essentially a synergistic event where the sum of two seemingly mild concussions combine to create an event that is potentially fatal. The findings during the autopsy are that there is insignificant damage to the brain to cause death. The damage that occurs, however, is on a molecular level causing a strain on the metabolic processes of the brain called dysautoregulation. Without an understanding of the changes that have occurred on a molecular level in SIS the assignment of cause and manner of death is difficult for the medical examiner. Currently, in order to diagnose SIS, a thorough scene investigation, along with the documentation of a previous head injury is needed. Without a full understanding of SIS and the pathophysiology changes that take place a medical examiner (ME) could misclassify the cause and manner of death in a death due to SIS. In the future, eliminating the prerequisite of identification and documentation of previous head injuries in order to diagnose SIS is needed. This paper evaluates the literature on the current knowledge of TBI and concussions in an attempt to create a protocol on how a medical examiner should approach a case where autopsy findings are unremarkable.