Associate Professor Andrew Gardner

© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. In the 20th century, chronic traumatic encephalopathy (CTE) was conceptualized as a neurological disorder affecting some active and retired boxers who had tremendous exposure to neurotrauma. In recent years, the two research groups in the USA who have led the field have asserted definitively that CTE is a delayed-onset and progressive neurodegenerative disease, with symptoms appearing in midlife or decades after exposure. Between 2005 and 2012 autopsy cases of former boxers and American football players described neuropathology attributed to CTE that was broad and diverse. This pathology, resulting from multiple causes, was aggregated and referred to, in toto, as the pathology ¿characteristic¿ of CTE. Preliminary consensus criteria for defining the neuropathology of CTE were forged in 2015 and published in 2016. Most of the macroscopic and microscopic neuropathological findings described as characteristic of CTE, in studies published before 2016, were not included in the new criteria for defining the pathology. In the past few years, there has been steadily emerging evidence that the neuropathology described as unique to CTE may not be unique. CTE pathology has been described in individuals with no known participation in collision or contact sports and no known exposure to repetitive neurotrauma. This pathology has been reported in individuals with substance abuse, temporal lobe epilepsy, amyotrophic lateral sclerosis, multiple system atrophy, and other neurodegenerative diseases. Moreover, throughout history, some clinical cases have been described as not being progressive, and there is now evidence that CTE neuropathology might not be progressive in some individuals. Considering the current state of knowledge, including the absence of a series of validated sensitive and specific biomarkers, CTE pathology might not be inexorably progressive or specific to those who have experienced repetitive neurotrauma.

Copyright © 2019 Journal of Orthopaedic & Sports Physical Therapy®. U SYNOPSIS: Sport-related concussion is common in full-contact and collision sports. Epidemiology studies use different types of surveillance systems and concussion definitions. Concussion incidence rates vary across age, sex, sport, and level of competition. Incidence rates are increasing, likely due to higher rates of reporting following improved knowledge and increased regulations. In this review, we summarize 7 key concepts related to concussion epidemiology: concussion definition, changes in concussion knowledge, reliability and accuracy of injury surveillance systems, conservative management and return to play, reliability of self-report, incidence of concussion across levels of play, and understanding the behaviors of players, coaches, and medical personnel from a multidisciplinary management perspective.

© 2019, American Psychiatric Association. All rights reserved. Objective: In recent years, it has been proposed that problems with anger control and depression define clinical features of chronic traumatic encephalopathy (CTE). The authors examined anger problems and depression in middle-aged men from the general population and related those findings to the proposed clinical criteria for CTE. Methods: A sample of 166 community-dwelling men ages 40¿60 was extracted from the normative database of the National Institutes of Health Toolbox. All participants denied prior head injury or traumatic brain injury (TBI). Participants completed scales assessing anger, hostility, aggression, anxiety, and depression. Results: In response to the item ¿I felt angry,¿ 21.1% of men reported ¿sometimes,¿ and 4.8% reported ¿often.¿ When asked ¿If I am provoked enough I may hit another person,¿ 11.4% endorsed the statement as true. There were moderate correlations between anger and anxiety (Spearman¿s r=0.61) and between depression and affective anger (r=0.51), hostility (r=0.56), and perceived hostility (r=0.35). Participants were dichotomized into a possible depression group (N=49) and a no-depression group (N=117) on the basis of the question ¿I feel depressed,¿ specific to the past 7 days. The possible depression group reported higher anxiety (p<0.001, Cohen¿s d=1.51), anger (p<0.001, Cohen¿s d=0.96), and hostility (p<0.001, Cohen¿s d=0.95). Conclusions: Some degree of anger and aggression are reported by a sizable minority of middle-aged men in the general population with no known history of TBI. Anger and hostility are correlated with depression and anxiety, indicating that all tend to co-occur. The base rates and comorbidity of affective dysregulation in men in the general population is important to consider when conceptualizing CTE phenotypes.

© 2017 Taylor & Francis Group, LLC. Primary Objective: This study reviewed the available sideline Sport Concussion Assessment Tool-Third Edition (SCAT3) performance of players who were removed from play using the ¿concussion interchange rule¿ (CIR), the available video footage of these incidences, and associated return to play and concussion diagnosis decisions. Research Design: Descriptive, observational case series. Methods and Procedures: Data were collected from all NRL players who used the CIR during the 2014 season. Main Outcomes and Results: Complete SCAT3 and video analysis data were available for 38 (23%) of 167 uses of the concussion interchange rule, of which 20 (52.6%) players were medically diagnosed with concussion. Those with video evidence of unresponsiveness performed more poorly on the modified Balance Error Scoring System (M-BESS; p¿=.04; Cohen¿s d¿=.69) and reported greater symptoms (p¿=.03; d¿=.51). Similarly, players with a vacant stare reported greater symptoms (p¿=.05; d¿=.78). Those who demonstrated three signs (unresponsiveness, vacant stare and gait ataxia) performed more poorly on the M-BESS (p¿=.03; d¿=¿1.4) and reported greater symptoms than those with no observable signs (p¿=.03; d¿=¿1.4). Conclusions: The SCAT3 is sensitive to the acute effects of concussion in professional athletes; however, a minority of injured athletes might go undetected by this test.

© Copyright 2017, Mary Ann Liebert, Inc. Risk factors for concussion in active-duty military service members are poorly understood. The present study examined the association between self-reported concussion history and genetics (apolipoprotein E [APOE], brain-derived neurotrophic factor [BDNF], and D2 dopamine receptor genes [DRD2]), trait personality measures (impulsive-sensation seeking and trait aggression-hostility), and current alcohol use. The sample included 458 soldiers who were preparing to deploy for Operation Iraqi Freedom/Operation Enduring Freedom. For those with the BDNF Met/Met genotype, 57.9% (11/19) had a history of one or more prior concussions, compared with 35.6% (154/432) of those with other BDNF genotypes (p = 0.049, odds ratio [OR] = 2.48). APOE and DRD2 genotypes were not associated with risk for past concussions. Those with the BDNF Met/Met genotype also reported greater aggression and hostility personality characteristics. When combined in a predictive model, prior military deployments, being male, and having the BDNF Met/Met genotype were independently associated with increased lifetime history of concussions in active-duty soldiers. Replication in larger independent samples is necessary to have more confidence in both the positive and negative genetic associations reported in this study.

© © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. Objective Systematic review of possible long-term effects of sports-related concussion in retired athletes. Data sources Ten electronic databases. Study selection Original research; incidence, risk factors or causation related to long-term mental health or neurological problems; individuals who have suffered a concussion; retired athletes as the subjects and possible long-term sequelae defined as >10 years after the injury. Data extraction Study population, exposure/outcome measures, clinical data, neurological examination findings, cognitive assessment, neuroimaging findings and neuropathology results. Risk of bias and level of evidence were evaluated by two authors. Results Following review of 3819 studies, 47 met inclusion criteria. Some former athletes have depression and cognitive deficits later in life, and there is an association between these deficits and multiple prior concussions. Former athletes are not at increased risk for death by suicide (two studies). Former high school American football players do not appear to be at increased risk for later life neurodegenerative diseases (two studies). Some retired professional American football players may be at increased risk for diminishment in cognitive functioning or mild cognitive impairment (several studies), and neurodegenerative diseases (one study). Neuroimaging studies show modest evidence of macrostructural, microstructural, functional and neurochemical changes in some athletes. Conclusion Multiple concussions appear to be a risk factor for cognitive impairment and mental health problems in some individuals. More research is needed to better understand the prevalence of chronic traumatic encephalopathy and other neurological conditions and diseases, and the extent to which they are related to concussions and/or repetitive neurotrauma sustained in sports.

© 2017 Elsevier Ltd Background Sports concussion is a risk for players involved in high impact, collision sports. Post-concussion, the majority of symptoms subside within 7¿10 days, but can persist in 10¿20% of athletes. Understanding the effects of sports concussion on sensorimotor systems could inform physiotherapy treatment. Objective To explore changes in sensorimotor function in the acute phase following sports concussion. Design Prospective cohort study. Methods Fifty-four players from elite rugby union and league teams were assessed at the start of the playing season. Players who sustained a concussion were assessed three to five days later. Measures included assessments of balance (sway velocity), vestibular system function (vestibular ocular reflex gain; right-left asymmetry), cervical proprioception (joint position error) and trunk muscle size and function. Results During the playing season, 14 post-concussion assessments were performed within 3¿5 days of injury. Significantly decreased sway velocity and increased size/contraction of trunk muscles, were identified. Whilst not significant overall, large inter-individual variation of test results for cervical proprioception and the vestibular system was observed. Limitations The number of players who sustained a concussion was not large, but numbers were comparable with other studies in this field. There was missing baseline data for vestibular and cervical proprioception testing for some players. Conclusions Preliminary findings post-concussion suggest an altered balance strategy and trunk muscle control with splinting/over-holding requiring consideration as part of the development of appropriate physiotherapy management strategies.

© 2015 Elsevier Ltd. Chronic traumatic encephalopathy (CTE) has been described in the literature as a neurodegenerative disease with: (i) localized neuronal and glial accumulations of phosphorylated tau (p-tau) involving perivascular areas of the cerebral cortex, sulcal depths, and with a preference for neurons within superficial cortical laminae; (ii) multifocal axonal varicosities and axonal loss involving deep cortex and subcortical white matter; (iii) relative absence of beta-amyloid deposits; (iv) TDP-43 immunoreactive inclusions and neurites; and (v) broad and diverse clinical features. Some of the pathological findings reported in the literature may be encountered with age and other neurodegenerative diseases. However, the focality of the p-tau cortical findings in particular, and the regional distribution, are believed to be unique to CTE. The described clinical features in recent cases are very similar to how depression manifests in middle-aged men and with frontotemporal dementia as the disease progresses. It has not been established that the described tau pathology, especially in small amounts, can cause complex changes in behavior such as depression, substance abuse, suicidality, personality changes, or cognitive impairment. Future studies will help determine the extent to which the neuropathology is causally related to the diverse clinical features.

© 2015, BMJ Publishing Group. All rights reserved. Objectives: Concussion remains one of the inherent risks of participation in rugby league. While other injuries incurred by rugby league players have been well studied, less focus and attention has been directed towards concussion. Review method: The current review examined all articles published in English from 1900 up to June 2013 pertaining to concussion in rugby league players. Data sources: Publications were retrieved via six databases using the key search terms: rugby league, league, football; in combination with injury terms: athletic injuries, concussion, sports concussion, sports-related concussion, brain concussion, brain injury, brain injuries, mild traumatic brain injury, mTBI, traumatic brain injury, TBI, craniocerebral trauma, head injury and brain damage. Observational, cohort, correlational, cross-sectional and longitudinal studies were all included. Results: 199 rugby league injury publications were identified. 39 (20%) were related in some way to concussion. Of the 39 identified articles, 6 (15%) had the main aim of evaluating concussion, while the other 33 reported on concussion incidence as part of overall injury data analyses. Rugby league concussion incidence rates vary widely from 0.0 to 40.0/1000 playing hours, depending on the definition of injury (time loss vs no time loss). The incidence rates vary across match play versus training session, seasons (winter vs summer) and playing position (forwards vs backs). The ball carrier has been found to be at greater risk for injury than tacklers. Concussion accounts for 29% of all injuries associated with illegal play, but only 9% of injuries sustained in legal play. Conclusions: In comparison with other collision sports, research evaluating concussion in rugby league is limited. With such limited published rugby league data, there are many aspects of concussion that require attention, and future research may be directed towards these unanswered questions.

© 2015, Mary Ann Liebert, Inc. Prognostic models can guide clinical management and increase statistical power in clinical trials. The availability and adequacy of prognostic models for mild traumatic brain injury (MTBI) is uncertain. The present study aimed to (1) identify and evaluate multivariable prognostic models for MTBI, and (2) determine which pre-, peri-, and early post-injury variables have independent prognostic value in the context of multivariable models. An electronic search of MEDLINE, PsycINFO, PubMed, EMBASE, and CINAHL databases for English-language MTBI cohort studies from 1970-2013 was supplemented by Web of Science citation and hand searching. This search strategy identified 7789 articles after removing duplicates. Of 182 full-text articles reviewed, 26 met eligibility criteria including (1) prospective inception cohort design, (2) prognostic information collected within 1 month post-injury, and (3) 2+variables combined to predict clinical outcome (e.g., post-concussion syndrome) at least 1 month later. Independent reviewers extracted sample characteristics, study design features, clinical outcome variables, predictor selection methods, and prognostic model discrimination, calibration, and cross-validation. These data elements were synthesized qualitatively. The present review found no multivariable prognostic model that adequately predicts individual patient outcomes from MTBI. Suboptimal methodology limits their reproducibility and clinical usefulness. The most robust prognostic factors in the context of multivariable models were pre-injury mental health and early post-injury neuropsychological functioning. Women and adults with early post-injury anxiety also have worse prognoses. Relative to these factors, the severity of MTBI had little long-term prognostic value. Future prognostic studies should consider a broad range of biopsychosocial predictors in large inception cohorts.

© 2014, Springer International Publishing Switzerland. Objective: The aim of the current review was to systematically evaluate the available evidence on concussion in Rugby Union and to conduct a meta-analysis of findings regarding the incidence of concussion.Background: Rugby Union, a popular full-contact sport played throughout the world, has one of the highest rates of concussion of all full-contact sports.Methods: Articles were retrieved via a number of online databases. The current review examined all articles published in English up to May 2014 pertaining to concussion in Rugby Union players. The key search terms included ¿Rugby Union¿, ¿rugby¿, ¿union¿, and ¿football¿, in combination with the injury terms ¿athletic injuries¿, ¿concussion¿, ¿sports concussion¿, ¿sports-related concussion¿, ¿brain concussion¿, ¿brain injury¿, ¿brain injuries¿, ¿mild traumatic brain injury¿, ¿mTBI¿, ¿traumatic brain injury¿, ¿TBI¿, ¿craniocerebral trauma¿, ¿head injury¿, and ¿brain damage¿.Results: The final search outcome following the eligibility screening process resulted in the inclusion of 96 articles for this review. The meta-analysis included a total of 37 studies. The results of the meta-analysis revealed an overall incidence of match-play concussion in men¿s rugby-15s of 4.73 per 1,000 player match hours. The incidence of concussion during training was 0.07 per 1,000 practice hours. The incidence of concussion in women¿s rugby-15s was 0.55 per 1,000 player match hours. In men¿s rugby-7s match-play, concussion incidence was 3.01 per 1,000 player match hours. The incidence of concussion varied considerably between levels of play, with elite level play recording a rate of 0.40 concussions per 1,000 player match hours, schoolboy level 0.62 concussions per 1,000 player match hours, and the community or sub-elite level recording a rate of 2.08 concussions per 1,000 player match hours. The incidence of concussion in men¿s rugby-15s as a function of playing position (forwards vs. backs) was 4.02 and 4.85 concussions per 1,000 player match hours, respectively.Conclusions: Concussion is a common injury sustained and reported in match play and to a lesser extent during practice by Rugby Union players. Based on the available published data, there appears to be a variation in risk of concussion across level of play, with the sub-elite level having the greatest incidence of injury. Future research focused on studying the acute consequences and best management strategies in current players, and the potential longer term outcomes of concussion in retired players, is needed. A focus on the areas of prevention, injury identification, and medical management, and risk for long-term outcomes will be of benefit to current athletes.

Traumatic brain injury (TBI) is a common condition that is often complicated by neuropsychiatric sequelae that can have major impacts on function and quality of life. An alteration in the sense of smell is recognized as a relatively common complication of TBI; however in clinical practice, this complication may not be sought or adequately characterized. We conducted a systematic review of studies concerned with olfactory functioning following TBI. Our predetermined criteria led to the identification of 25 studies published in English, which we examined in detail. We have tabulated the data from these studies in eight separate tables, beginning with Table 1, which highlights each study's key findings, and we provide a summary/synthesis of the findings in the accompanying results and discussion sections. Despite widely differing methodologies, the studies attest to a high frequency of post-TBI olfactory dysfunction and indicate that its presence can serve as a potential marker of additional structural or functional morbidities. © 2014 Schofield, Moore and Gardner.