A REVIEW OF TRAUMATIC BRAIN INJURY AND NEURODEGENERATIVE CHANGES IN NFL PLAYERS By Mya Bui William Callison Katie Childs Luke DeMarco Sydney Flynn Jacob Garza Megan Griffin Addie Long Sarah Luey Erick Porto Joanna Riegert Vicki Wetzel A thesis submitted to the School of Radiologic Sciences in collaboration with a research agenda team In partial fulfillment of the requirements for the degree of MASTER OF SCIENCE IN RADIOLOGIC SCIENCES (MSRS) WEBER STATE UNIVERSITY Ogden, Utah December 16, 2022 THE WEBER STATE UNIVERSITY GRADUATE SCHOOL SUPERVISORY COMMITTEE APPROVAL of a thesis submitted by Mya Bui William Callison Katie Childs Luke DeMarco Sydney Flynn Jacob Garza Megan Griffin Addie Long Sarah Luey Erick Porto Joanna Riegert Vicki Wetzel This thesis has been read by each member of the following supervisory committee and by majority vote found to be satisfactory. ______________________________ Dr. Robert Walker, PhD Chair, School of Radiologic Sciences ______________________________ Dr. Laurie Coburn, EdD Director of MSRS RA ______________________________ Dr. Tanya Nolan, EdD Director of MSRS ______________________________________________________________________ Christopher Steelman, MS Director of MSRS Cardiac Specialist THE WEBER STATE UNIVERSITY GRADUATE SCHOOL RESEARCH AGENDA STUDENT APPROVAL of a thesis submitted by Mya Bui William Callison Katie Childs Luke DeMarco Sydney Flynn Jacob Garza Megan Griffin Addie Long Sarah Luey Erick Porto Joanna Riegert Vicki Wetzel This thesis has been read by each member of the student research agenda committee and by majority vote found to be satisfactory. Date December 16, 2022 ____________________________________ Mya Bui December 16, 2022 ____________________________________ William Callison December 16, 2022 ____________________________________ Katie Childs December 16, 2022 ____________________________________ Luke DeMarco December 16, 2022 ____________________________________ Sydney Flynn December 16, 2022 ____________________________________ Jacob Garza December 16, 2022 ____________________________________ Megan Griffin December 16, 2022 ____________________________________ Addie Long December 16, 2022 ____________________________________ Sarah Luey December 16, 2022 ____________________________________ Erick Porto December 16, 2022 ____________________________________ Joanna Riegert December 16, 2022 ____________________________________ Vicki Wetzel Acknowledgments We would like to acknowledge and express our deepest gratitude to Dr. Laurie Colburn for her guidance and dedication through all phases of writing this Master’s Thesis. Thank you to all the outstanding faculty and staff for the support and knowledge they have graciously provided throughout our continuing education here at Weber State University. Dr. Robert Walker, along side his colleagues have made the radiology program at Weber State one of the premier institutions in the nation. We also give special thanks to all our family and friends who have been there every step of the way along this journey. They have been our rock, our foundation, and our biggest supporters. We dedicate this paper to those who have suffered and still suffer from the debilitating effects of traumatic brain injuries and dealing with the potential ramifications of developing chronic traumatic encephalopathy. Also, to the ones who have continually cared for them along their path of healing. Abstract Traumatic brain injury (TBI) is by definition, a disruption of normal brain function, caused by an external and often violent physical force. TBI’s do not discriminate as they can exert their effects regardless of race, gender, or age. These types of injuries have been associated with severe cognitive and behavioral disabilities and even death on a worldwide scale. We will examine the role of TBI’s, and the long-term ramifications on humans specifically, past NFL football players. Several common themes became apparent throughout our research and were elaborated upon further in this study. TBI’s affect NFL players with varying degrees either during or post NFL career. In this study, a synthesis of previously reported data was used to identify and further characterize TBI in early stages, recognize potential causes, and find techniques to decrease future occurrences. We also attempted to ascertain if a relationship between TBI’s and Chronic Traumatic Encephalopathy (CTE) could be established, with a primary focus on NFL players, that were the target of this research paper. Above all, the purpose of this study was designed to raise awareness of recurrent TBI’s and their overall effect on NFL players well-being and the implications of suffering multiple TBIs with an emphasis on long term mental health. This scoping review will be evaluating targeted, well defined research questions and examining data related to TBI’s and NFL players. Specifically, what is a TBI and how is it diagnosed? What are symptoms and side effects of a TBI? Is there a threshold of injury resulting in a TBI? And finally, do multiple TBI’s lead to CTE? A scoping review of scholarly databases, peer reviewed journals, medical records, and autopsy reports highlighted repetitive, key terms as stated throughout this analysis. The targeted subject base will be male NFL players that played between 2007 and 2017. But the data compiled will serve as a measure for all those who have suffered and might suffer from a TBI. Currently, there is no concrete data to prove our hypothesis that there is a direct link between TBI and CTE. However, after reviewing over one hundred and sixty, scholarly, peer review journals, the probability that a person will suffer from long term effects after sustaining a TBI is well established. The provided information suggests a strong correlation between TBI and CTE. With cutting edge and innovative technological advances, the ability of researchers and physicians to anticipate and possibly prevent the debilitating disease known as CTE is only a matter of time. Due to the nature of the NFL, head injuries are a common and unavoidable occurrence among players. Therefore, keeping a pulse on the newest technology, concussion evaluation surveillance, and diagnosis at the time of injury is key when keeping players’ safety in mind. By using these principles as a measure of precedent, we aim limit the occurrences and potential harmful effects of TBI. Perhaps even more vehement is the need to discern whether these types of injuries lead to behavioral alterations and subsequent changes in a person’s mental health. Chapter Chapter Chapter 1 – Introduction Introduction Introduction IntroductionIntroductionIntroduction Introduction BackgroundBackground BackgroundBackground Background BackgroundBackground Traumatic TraumaticTraumatic brain brainbrain injury injury injuryinjury (TBI)(TBI) (TBI) is a growing growing growing public public health healthhealth health concernconcern concernconcern that cancancan oftenoften often be referredreferredreferred referred referredreferred to as the “silent “silent “silent “silent epidemic”. epidemic”. epidemic”. epidemic”. It is estimatedestimated estimated estimated that there there are are more more than one one million million millionmillion emergencyemergency emergencyemergencyemergencyemergencyemergency department department department department (ED) (ED)(ED) visits visits for head headhead injury injury injury eacheacheacheach yearyearyearyear in the US, with approximatelyapproximately approximately approximatelyapproximatelyapproximatelyapproximatelyapproximately 300,000 300,000 300,000 resulting resulting resulting hospitalizations. hospitalizations. hospitalizations.hospitalizations. i TBI cancancan be defined defineddefined defined as the disr uption uption in brain brainbrain function,function, function, or other other evidence evidence of brain brain pathology pathology pathology pathology causedcausedcaused causedcaused by an externalexternalexternal external external physical physicalphysical physicalphysicalphysical force, force,force,force,ii ,iii ,iv andand is the greatest greatestgreatestgreatestgreatest contributorcontributorcontributor contributor to worldwide worldwide death deathdeath andand disability. disability. disability.disability. It has has been beenbeen documented documenteddocumented documented that TBI affectsaffects affectsaffectsaffects Children,Children, Children, Children, Young adults,adults, adults, andand adultsadults adults over over ageage 60 significantly significantly significantlysignificantly significantly more more than anyanyany other traumatictraumatic traumatic injury. injury. injury.injury. PhysicalPhysicalPhysicalPhysical Physical trauma trauma trauma to the head headhead or neck, neck,neck, with eveneven even minimalminimal minimal minimal force, force,force,force, has has the potential potential of causingcausingcausing causing a TBI.TBI.TBI.TBI. The suddensudden sudden movements movements that causecausecause the the brain brain to impact impact impactimpact the skull skull with anyanyany typetypetype of forceful forcefulforcefulforceful forceful accelerationaccelerationaccelerationaccelerationaccelerationaccelerationacceleration acceleration acceleration or rotation rotation rotation causescausescauses causes a physiological physiologicalphysiological physiological physiological physiologicalphysiological andand chemicalchemicalchemicalchemical chemicalchemicalchemical reaction, reaction,reaction,reaction,reaction, in effecteffect effecteffecteffect altering,altering, altering,altering, altering,altering, stretching, stretching,stretching, stretching, andand damaging damaging damagingdamaging brainbrain brain cells.cells.cells. cells. v,vi Debates Debates Debates currentlycurrently currentlycurrently currently range rangerangerange acrossacrossacross medical medicalmedical providers, providers, providers, clinicalclinical clinical clinical researchers researchersresearchersresearchersresearchersresearchersresearchers researchers andand neurological neurological neurologicalneurological neurologicalneurological interventionalists interventionalistsinterventionalists interventionalists interventionalists interventionalists interventionalists aboutabout the symptomatsymptomatsymptomat symptomat ology, ology,ology,ology, mechanism mechanism mechanism of injury, injury, injury,injury, andand clinicalclinical clinical clinical definition definition definition of TBI. TBI. CharacterizationCharacterization Characterization CharacterizationCharacterization Characterization CharacterizationCharacterization Characterization of the term term “concussion” “concussion” “concussion” “concussion” “concussion” “concussion” currentlycurrentlycurrently currentlycurrently currently has has no internationally internationallyinternationally internationallyinternationally internationally internationally internationally agreedagreed agreed upon standard standard within within the healthcare healthcarehealthcare healthcare healthcarehealthcare community.community. community. community.community. Thus, clinicalclinical clinical clinical diagnosis diagnosisdiagnosis andand management management management management of TBITBITBI andand concussionsconcussions concussions concussions areare oftenoften often subjective subjective subjective subjective andand open open to interpretation interpretationinterpretationinterpretation interpretation by the the provider. provider. The terms termsterms concussionconcussion concussion concussion andand TBITBITBI areare oftenoften often used used interchangeably, interchangeably,interchangeably, interchangeably,interchangeably,interchangeably,interchangeably,interchangeably,interchangeably,interchangeably, interchangeably, when when in fact factfact they they areareare notnot alwaysalways alwaysalways synonymous.synonymous.synonymous. synonymous.synonymous. synonymous. This scientific scientific scientific confusionconfusion is reflected reflected reflectedreflected by the factfactfactfact that TBITBITBI hashashas been beenbeen defined defined more than 40 different differentdifferentdifferentdifferent ways waysways in the scientific scientific literature. literature. literature.literature. literature.literature.viiviivii TBIs TBIs cancancan affectaffectaffect affectaffect anyanyany individual individual regardless regardlessregardlessregardless regardlessregardless of ageageage or sex. sex.sex. However, However,However, However, epidemiologicalepidemiological epidemiological epidemiological epidemiological datadatadata shows that adultadult men areare approximately approximately approximately approximately 40% more likely likely likely to suffer suffersuffer a TBITBITBI comparedcomparedcompared comparedcompared to adultadult women. women. viiiviiiviiiviii,ix ,x Men Men areare more more likely likely likelylikely to sustain sustainsustain head headhead trauma traumatrauma from from combatcombat -related related related injuries,injuries, injuries, contactcontact contact sports, work work-related relatedrelatedrelated injuries, injuries, injuries, falls, falls, falls, andand motor motor vehicle vehicle vehiclevehicle collisions.collisions. collisions. collisions. Many ManyMany studies studies have have linked linked linked repeatrepeatrepeat repeatrepeat occurrences occurrencesoccurrences occurrencesoccurrences occurrencesoccurrences of TBIsTBIsTBIsTBIs to the development development development developmentdevelopment of chronicchronic traumatic traumatic traumatic encephalopathyencephalopathy encephalopathyencephalopathy encephalopathy encephalopathy (CTE), (CTE), especiallyespecially especiallyespecially especially in NFL players. players.players.players. RecentRecentRecentRecentRecent datadata acquisitionacquisitionacquisition acquisition acquisition andand high highhigh-profile profile profile incidents incidents have have spurred spurred spurredspurred awarenessawareness awareness campaigns,campaigns,campaigns, campaigns,campaigns,campaigns, media media discussions, discussions, discussions, andand updating updating public public health health policies policies policies aroundaroundaround TBI and the the potential potential for residual residual long long-term term effectseffectseffectseffectseffectseffects such such as CTE.CTE. StatementStatement StatementStatementStatementStatementStatement of ProblemProblemProblem Problem Problem Tr aumaticaumatic brain brainbrain injury injury injuryinjury (TBI)(TBI) (TBI) can be a severe, severe,severe,severe, severe, long long-term term injury injury injury that thatthat affectsaffects affectsaffectsaffects many many NFLNFLNFL football football players playersplayersplayers throughout throughoutthroughout throughout their careers.careers.careers.careers.careers.careers. Dissecting DissectingDissecting Dissecting the occurrence,occurrence,occurrence,occurrence, occurrence, occurrence, occurrence,occurrence, prevalence, prevalence,prevalence,prevalence, prevalence, prevalence,prevalence, and history history history of TBI will provide betterbetterbetter betterbetter mitigation mitigation mitigationmitigationmitigation mitigation techniques techniques to prevent prevent prevent injuries. injuries. injuries. TBITBITBI is pr evalentevalent evalent within within the NFL organization, organization, organization, organization,organization, organization, jeopardizing jeopardizingjeopardizing jeopardizing athletesathletes athletesathletes ’ abilityability ability ability to perform perform perform at a professional professionalprofessional professional professional level level andand putting putting their long -termtermterm neurological neurological neurologicalneurologicalneurologicalneurologicalneurological health healthhealth health at risk. TBITBITBI hashashas impacted impacted the NFL NFL by consistentlyconsistently consistently consistently makingmakingmaking the the organization organization organizationorganization organization revamp revamp revamp athleteathlete athleteathlete concussionconcussion concussion concussion proto colscols to slowslow slow down the neuro neuro -degenerationdegenerationdegeneration degeneration degenerationdegenerationdegeneration degeneration athletesathletes athletesathletes areare experiencing.experiencing.experiencing. experiencing. experiencing.experiencing.experiencing. experiencing.experiencing. In conductingconducting conducting conducting conducting a scopingscopingscoping review, review, review, information information will be extrapolatedextrapolatedextrapolated extrapolated extrapolated from from a vastvastvast amountamount of scholarly scholarly scholarlyscholarly researchresearchresearch researchresearch research articles.articles. articles. This information informationinformationinformation information will demonstrate demonstrate demonstrate demonstrate how to recognize recognize recognizerecognize recognizerecognize andand characterizecharacterize characterize characterizecharacterize characterize characterize TBITBITBI in the earlyearlyearly early stage stagestagestage of the disease diseasediseasedisease process processprocess to identify identify a root causecausecause and preventionprevention preventionpreventionprevention prevention techniques. techniques. This review review review will will alsoalso examineexamineexamineexamine examine the potential potentialpotential potentialpotential correlationcorrelation correlationcorrelation between between betweenbetween TBI and and the manifestation manifestationmanifestation of CTE.CTE. PurposePurposePurposePurposePurpose The purpose purpose of this this researchresearchresearch researchresearch research study study is to raiseraiseraise awar awar enesseness eness aboutabout recurrent recurrentrecurrent recurrentrecurrent TBIs TBIsTBIs andand the potential long -term term effectseffects effectseffectseffectseffects on players playersplayersplayers in the NFL.NFL.NFL.NFL. In addition, addition, addition, addition, we aimaim to determine determine determine determine if a direct directdirect link link can be establishedestablished established established betweenbetweenbetween betweenbetween TBITBITBI andand subsequent subsequentsubsequent behavior behavior changeschangeschangeschangeschangeschangeschanges in thethe connectionconnection connectionconnection connection with the development development development developmentdevelopment of CTECTE in formerformer former NFL players. players.players.players. This review review included included malesmalesmales that thatthat played playedplayedplayed in the NFLNFLNFL in the United StatesStates States between between betweenbetween the yearsyearsyearsyears of 2007 andandand 2017. Our thesis will evaluateevaluate evaluate andand discuss whatwhat what constitutesconstitutes a traumatic traumatic traumatic brain brainbrain injury, injury,injury, whatwhat what rolerole medical medical imaging imaging imaging plays playsplays in diagnosis, diagnosis,diagnosis, andand the phy physiopathology siopathologysiopathologysiopathology of TBITBITBI on the brain. brain. We will alsoalso assessassess what what typestypestypes types of injuries injuries injuries lead to TBI,TBI,TBI,TBI, methods of prevention, prevention, prevention, prevention, andand the impacts impacts impactsimpacts of chronicchronic traumatic traumatic encephalopathyencephalopathy encephalopathyencephalopathy encephalopathy encephalopathy on a player’s player’s player’s player’s player’s player’s physical physicalphysical physical andand mental mental health. health.health. health. It is our hope hope that by performingperformingperforming performing a scopingscopingscoping revi revi ew of this this data, data, we will conveyconvey conveyconvey the the importance importance importance importance of following following safetysafety safety safety protocols protocols andand practicespractices practicespractices practicespracticespractices as well well as the needneedneedneed forfor monitoring monitoring the long -term term effectseffects effectseffectseffects of TBITBITBI on NFL players. players.players.players. WithWith With the the information information currentlycurrently currently currently currently availableavailable available availableavailable andand statistics statistics statisticsstatistics synthesizedsynthesizedsynthesized synthesizedsynthesized from from various various peer peerpeer reviewedreviewedreviewed reviewedreviewed andand scholarly scholarly scholarlyscholarly scholarly sources, sources, sources,sources, our our intention intentionintention intention is to bring awarenessawareness awarenessawarenessawareness awareness of this this topic topic to the forefront forefrontforefrontforefront of player playerplayerplayer healthhealthhealthhealth health andand safety. safety.safety.safety.safety.safety. We believe believe believebelieve that accurateaccurateaccurateaccurate accurateaccurate discernment discernment discernment of this this information information is paramount paramount paramount for thethe health of the players, players,players,players, theirtheir their loved loved ones, ones, andand for future future generations generations generationsgenerationsgenerations generations to come. come. Research Research Research ResearchResearch Question(s) Question(s)Question(s) Question(s) TBI in NFLNFLNFL players: players:players:players: WhatWhat What is TBI? TBI? How is it assessed assessed assessed / diagnosed diagnosed diagnoseddiagnosed andandand what what role does does imaging imagingimagingimaging imaging play play in the diagnosis? diagnosis?diagnosis?diagnosis? diagnosis? WhatWhat What areare the side effects,effects, effects,effects,effects, symptoms,symptoms,symptoms, symptoms, treatments, treatments,treatments, treatments,treatments, andand the causativecausativecausative causative causative typestypestypes types of injury? njury?njury? Is there there a threshold threshold threshold for for sustaining sustainingsustaining sustaining an injury injury injury resultingresultingresulting resulting in TBI? TBI? WhatWhat What steps can be taken takentaken to prevent prevent prevent it andand does does multiple multiple multiple TBI lead leadlead to CTE?CTE? Nature NatureNatureNature of StudyStudy Study We chosechose to do a scopingscoping scopingscoping reviewreviewreview for for this this paper. paper. paper. ScopingScopingScoping reviewsreviewsreviews reviews areare exploratoryexploratoryexploratory exploratory exploratory exploratory research researchresearchresearchresearchresearchresearch pr ojects ojects that systematicallysystematicallysystematically systematicallysystematically systematicallysystematicallysystematically map literature literature literatureliterature literature on a topic topic by looking lookinglooking at existingexistingexisting existing andand emerging emergingemerging emerging data datadata through through identifying identifyingidentifying identifying key key concepts,concepts, concepts, concepts, concepts,concepts, theories, theories, andand sources sources sourcessources of evidenceevidence evidence that inform inform practice practice practicepractice in a field. field. Our review review reviewreview waswaswas guidedguided guided guided by five processes: processes:processes:processes: (a)(a)(a) identify identify identifyidentify the res researchearchearch earch question questionquestion question andand domain to be explored,explored,explored, explored, (b) locate locatelocate relevant relevant relevant studies, studies,studies, (c) (c) select selectselectselectselect relevantrelevantrelevant relevant studies studiesstudies based based based on predetermined predetermined predetermined predetermined predetermined inclusion/exclusion inclusion/exclusion inclusion/exclusioninclusion/exclusioninclusion/exclusion criteria,criteria,criteria, criteria, criteria, (d)(d) extrapolate,extrapolate,extrapolate, extrapolate, extrapolate, extrapolate, organize, organize, organize, organize,organize,organize, andand analyzeanalyze analyzeanalyzeanalyzeanalyze data data fromfromfromfrom relevantrelevantrelevant relevant relevant studies studies selected, selected, selected, (e)(e)(e) summarize summarizesummarize summarize andand report report the results.results.results. results. A standardized standardized standardizedstandardized andandand methodical methodical search searchsearchsearchsearch of scholarly scholarly scholarlyscholarly databasesdatabasesdatabases databasesdatabasesdatabases was was performed performed performed performed (i.e. (i.e.(i.e. PubMed,PubMed, PubMed, Google Google Scholar,Scholar,Scholar, Scholar,Scholar,Scholar, ScienceScienceScience Science Direct, Direct,Direct,Direct, NCBI, NCBI,NCBI, MEDLINE, MEDLINE, MEDLINE, MEDLINE, PLOSONE).PLOSONE).PLOSONE). PLOSONE). The remainder remainderremainder remainder of the data data was was collectedcollected collectedcollectedcollected through through surveys, surveys,surveys, medical medicalmedical records,records,records,records, records, interviews, interviews,interviews, interviews, an d autopsyautopsy autopsyautopsy reports.reports.reports. There ThereThere is a large large population of individuals individuals at risk for TBITBITBI andand CTE;CTE; however, however, however, those that did not participate participate participate in the NFL or werewerewerewere outside outside of the designated designated designateddesignated designateddesignateddesignated date date range rangerangerange werewerewere not included includedincluded in this this study. study.study. The The studies studiesstudies assessedassessed assessed were were evaluatedevaluatedevaluatedevaluated evaluated base base d on keykeykey terms, terms, repetitive repetitive repetitive repetitive themes, themes, andandand commoncommon common research research researchresearch research methods. This study study will utilize utilize utilizeutilize information information gatheredgatheredgathered gatheredgathered from from multiple multiple multiple sources sourcessources that evaluateevaluate evaluate guidelinesguidelines previously previouslypreviously previouslypreviously setsetset forth forth regarding regardingregardingregarding regarding the optimal optimal diagnosis diagnosis diagnosis diagnosisdiagnosis andand managementmanagementmanagement managementmanagementmanagement of TBI, TBI, but they they mus t be taken taken in contextcontext context of the situation situation situation situation andand cannotcannotcannot cannot be used used in everyevery everyevery individual individual individual individual circumstance circumstance circumstancecircumstance circumstance since eacheacheacheach TBI, TBI,TBI, andand everyevery everyevery individual individual is unique. EvolutionEvolution Evolution of clinicalclinical clinical clinical diagnosis diagnosisdiagnosis andand management managementmanagementmanagement has has made substantial substantialsubstantial substantialsubstantial gainsgainsgainsgains with the development development development developmentdevelopment of the Glasgow GlasgowGlasgowGlasgow ComaComa Sc aleale (GCS) (GCS)(GCS)(GCS) andand the PostPost Traumatic TraumaticTraumatic Amnesia Amnesia (PTA) scale. scale.scale. ImagingImagingImagingImagingImaging Imaging modalities modalities such such as ComputedComputed ComputedComputed Tomography Tomography TomographyTomographyTomography (CT) andand Magnetic MagneticMagneticMagneticMagnetic Magnetic ResonanceResonanceResonance Resonance Resonance (MRI) (MRI)(MRI)(MRI) areare at the forefront forefrontforefront forefront of innovation andand evaluation,evaluation, evaluation, evaluation, which which aidsaids diagnosis diagnosis diagnosis andand treatment. treatment.treatment.treatment. treatment.treatment. New cuttingcutting cutting cutting-edgeedgeedge clinicalclinical clinical clinical tests th at analyzeanalyze analyzeanalyzeanalyzeanalyze physiopathology physiopathologyphysiopathology physiopathology physiopathology physiopathology physiopathology on a cellularcellularcellular cellular andand molecular molecularmolecularmolecular level level level areare currentlycurrently currentlycurrently currently in development developmentdevelopmentdevelopmentdevelopment andand can be beneficial beneficial beneficialbeneficial beneficial when the resultsresultsresults results of other diagnostic diagnosticdiagnostic diagnostic tests areare inconclusive inconclusive inconclusive or not readily readilyreadily readily available.available. available. available.available. These These can deliver deliver deliver deliver quantifiable quantifiable quantifiable quantifiable metrics metrics related related related to TBITBITBI with the use of biofluid biofluid andand biomarker biomarkerbiomarker biomarker testing testing andand will will be discussed discusseddiscussed discusseddiscussed further further in this this paper. paper. paper. SignificanceSignificance SignificanceSignificanceSignificance of StudyStudy StudyStudy WithWith more more focusfocus focus on TBI's TBI'sTBI's short short- andand long -term termterm effectseffectseffectseffectseffectseffects (especially(especially(especially (especially(especially (especially (especially amongamong among NFLNFL players), players),players),players),players), players), aggressiveaggressive aggressive aggressive andandand thorough thoroughthorough research researchresearch research research is in high high demand.demand.demand. demand. The The NFL hashashas highlighted highlightedhighlighted highlightedhighlighted highlightedhighlighted the need needneed andand significance significance significancesignificancesignificancesignificance of researching researching researchingresearchingresearchingresearching how TBITBITBI affectsaffects affectsaffectsaffects its players playersplayersplayers andand their theirtheir families. families. families. families.families. Decade DecadeDecadeDecadeDecade-long long studies studiesstudies have have been beenbeen conductedconducted conductedconductedconducted amongamongamong NFLNFLNFL players playersplayersplayers to determine determine determine determine how, why, why,why, andand what what factors factorsfactors contributecontribute contribute to TBI. TBI. Also, what whatwhat impacts impacts impactsimpacts traumatic traumatic traumatic brain rain injuries injuries injuries havehavehave on the neurological neurologicalneurological neurologicalneurologicalneurologicalneurological qualityquality quality qualityquality of living living for players playersplayersplayers past past their NFLNFLNFL careers.careers.careers. careers.careers. The NFL andand its operations operations operations operations areare accessedaccessedaccessedaccessedaccessed andand viewed viewedviewedviewed by millions millions millions worldwide worldwide worldwide everyevery everyevery week. week.week. TV networks, networks, networks, apparelapparel apparelapparel apparel shops, shops, andand many many other facetsfacetsfacetsfacetsfacets of the financial financial financial juggernaut juggernaut juggernautjuggernautjuggernaut juggernaut that is the NFL thrive on the commercecommerce commercecommercecommercecommerce within within within these sectors. sectors.sectors. PlayerPlayer PlayerPlayerPlayer health andand safetysafetysafety safetysafety areare paramountparamountparamount paramount to maintaining the NFLNFLNFL "brand""brand" "brand""brand" from from both a business business businessbusiness andand a humanitarian humanitarian standpoint. standpoint. standpoint. RecentRecentRecentRecentRecent studies studiesstudies have have shown a direct directdirectdirect link link between sub concussiveconcussive concussive concussive impacts,impacts, impacts, severeevere evereevere TBI, TBI,TBI, andand thethe probability probability probability probability of sustaining sustainingsustaining sustaining long -term term damage. damage.damage.damage. damage. The NFLNFLNFL hashashas spent spent a greatgreatgreat great deal dealdeal of money money to addressaddress address this this issue issue to improve improve player playerplayerplayer safety safety safetysafety andandand prevent prevent prevent potentially potentially careercareercareer careercareer-ending endingending injuries. injuries. injuries. Additionally, Additionally, Additionally, Additionally,Additionally, neurological neurologicalneurological neurologicalneurologicalneurologicalneurological function function function is drastically drastically drasticallydrasticallydrastically drastically affecteaffecteaffecteaffecteaffecteaffecte d by TBI,TBI,TBI,TBI, thus prompting prompting prompting immediate immediate immediate andand effectiveeffective effectiveeffectiveeffective effective changes changes employedemployed employedemployedemployedemployed by the the NFL. NFL. Marketing Marketing Marketing MarketingMarketing andand advertisingadvertising advertisingadvertising advertising campaignscampaignscampaigns campaignscampaigns such such as PlayPlay Play Smart,Smart, Smart, xi have have been beenbeen developeddevelopeddeveloped developed developed developed to raise raise awarenessawareness awarenessawarenessawareness awareness of this this topic. topic.topic. ResearchResearch Research into into how to best bestbest prevent prevent prevent andand establishestablish establishestablish establish thresholds thresholds thresholds for dia gnosisgnosis gnosis has has been beenbeen implemented. implemented. implemented. ReformedReformedReformed Reformed concussionconcussion concussion concussion evaluationevaluation evaluationevaluation evaluation evaluation andand "return"return"return"return to play" play"play" protocols protocols have havehave been beenbeen set set in place place for players playersplayersplayersplayers suspected suspected suspectedsuspected of sustaining sustainingsustaining sustainingsustaining a TBITBITBI during during a game.game.game. Video Video reviews reviews reviews of violent violentviolent hits hits suspicious suspicioussuspicious for TBI cancancan be further further furtherfurther scrutinized, scrutinized, scrutinized,scrutinized,scrutinized, andand play player assessmentassessment by an independent independentindependent neurologist, neurologist, neurologist, neurologist, who is on hand hand at everyevery everyevery game. game. These TheseThese protocols protocols help help ensureensure a playerplayer playerplayerplayer does does not returnreturnreturn to actionactionaction action unless clearedcleared clearedclearedcleared by a medicalmedicalmedical medical provider, provider, thus thus preventing preventing preventing preventing further further further injury. injury. injury.injury. InnovationsInnovations InnovationsInnovations Innovations in protective protectiveprotective protective headgear headgearheadgearheadgearheadgearheadgearheadgear have have been beenbeen des designed,igned,igned, igned, tested, tested,tested, andandand implemented, implemented, implemented, implemented, to thwart thwart the risks risks of TBI. TBI.TBI. Currently, Currently,Currently, Currently,Currently, the NFLNFL is in thethe process process processprocess of changingchanging changingchangingchanging changing the the tackling/hitting tackling/hitting tackling/hittingtackling/hittingtackling/hitting tackling/hitting tackling/hitting rulesrules rules as wellwellwell as the stance stance stance at the line line of scrimmage scrimmage scrimmagescrimmagescrimmage rules. rules. CuttingCutting Cutting -edgeedgeedgeedge technologytechnologytechnologytechnology technology technology allowsallows allows for for real realreal-time data data analysis,analysis, analysis,analysis,analysis, analysis, such such as putting putting sensors sensors in helmets helmets helmetshelmetshelmets andand mouthpieces mouthpieces mouthpiecesmouthpieces to increase increaseincreaseincrease awarenessawareness awarenessawarenessawareness awareness or indicate indicateindicateindicate a player playerplayerplayerplayer potentially potentially sustaining sustainingsustaining sustaining a TBI.TBI.TBI.TBI. All of thesethese these will be discussed discussed further further further later later in this this paper. paper.paper.paper. Monitoring Monitoring andand evaluatingevaluating evaluating evaluating potential TBI TBI of players playersplayersplayers at the time of injury injury injury has has proven roven to lessen lessen the effects effectseffects effects of TBITBITBI andand is currentlycurrently currentlycurrently currently the bestbestbest way way to protect protectprotect NFLNFLNFL players. players.players.players. Definition DefinitionDefinition Definition of TermsTermsTermsTermsTerms Acute Acute ConcussionConcussion Concussion Concussion Evaluation Evaluation EvaluationEvaluation Evaluation (ACE) (ACE)(ACE) - The ACE is an innovative assessmentassessment assessment tool that can be used used for the the initial initial initialinitial evaluationevaluation evaluation andand diagnosis diagnosis diagnosis of people people with a known or suspectedsuspected suspectedsuspected concussionconcussion concussionconcussion concussion or mild TBI. TBI.xiixiixii Alzheimer's Alzheimer's Alzheimer's Alzheimer'sAlzheimer's Alzheimer's Diseases DiseasesDiseases Diseases (AD) (AD) - AD is a progressiveprogressive progressiveprogressive progressive progressive disease disease beginning beginningbeginning beginningbeginning with mild memory memory loss andand can lead lead to the inabilityinability inability inability inability to carrycarrycarrycarrycarry out daily daily daily activitiesactivitiesactivities activities activities andand conversations.conversations. conversations. conversations. conversations. This This is the most commoncommon common form form of demen demen tia.tia. It waswaswas named named afterafter after Dr. Dr. Alois Alzheimer Alzheimer Alzheimer AlzheimerAlzheimer in 1906. xiiixiiixiiixiii BloodBlood BrainBrain Brain BarrierBarrierBarrier BarrierBarrierBarrier (BBB)(BBB)(BBB)(BBB)(BBB) - BloodBlood vessels vessels that that vascularizevascularizevascularize vascularize vascularize vascularize the CentralCentralCentral Central Nervous Nervous Nervous SystemSystemSystem have have unique properties propertiesproperties properties that thatthat allowallow allow these vessels vessels to tightlytightly tightly tightly regulate regulateregulate the the movement movement of molecules, molecules,molecules,molecules, ions, andand cellscellscells cells betw betw eeneeneen the blood andand the brain. brain. TheThe blood brain brain barrier barrierbarrier barrier alsoalso protects protectsprotects neural neural neuralneural tissue tissue from from toxins toxins andand pathogens. pathogens. pathogens.pathogens. xivxivxiv BrainBrain Brain InjuryInjury InjuryInjury Causes:Causes:Causes: Causes: A brain brain injury injury injury is causedcausedcaused caused when whenwhen an externalexternalexternal external external force forceforce disrupts disrupts normal normal brain brain function. function. function. This can be from from a blow to the head,head,head,head, suddensudden sudden accelerationccelerationccelerationcceleration ccelerationcceleration cceleration and/orand/orand/or deceleration, deceleration, deceleration, deceleration, deceleration, deceleration, pressure pressure from from an explosiveexplosiveexplosive explosive blast, or penetrating penetrating penetrating penetratingpenetrating penetrating injury. injury. injury.injury.xv ,xvi ClosedClosed Head HeadHead Trauma TraumaTrauma (CHT) (CHT) (CHT) -ClosedClosed Head HeadHead InjuryInjury Injury Injury (CHI), (CHI),(CHI), when when there therethere is no violation violationviolation violation of the skull or dura dura mater. mater. mater.mater. TheseThese These injuries injuries areareare classifiedclassified classified classified as concussion,concussion, concussion, contusion,contusion, contusion, diffuse diffusediffuse axonalaxonalaxonal axonal injury, injury, injury,injury, andand intracranial intracranialintracranialintracranialintracranialintracranialintracranial hematomahematomahematoma or hemorrhage. hemorrhage. hemorrhage. hemorrhage.hemorrhage.hemorrhage.xviixviixviixvii,xviiixviiixviiixviiixviii CentralCentralCentral Central Nervous Nervous SystemSystemSystemSystem (CNS) - The CNSCNS comprises comprisescomprises the brain brain andand spinal cord.cord. The CNSCNS is the body's body'sbody'sbody's processingprocessing processingprocessingprocessing centercentercenter centercenter made made of neurons. neurons.neurons.neurons. It controlscontrols controls most functions, functions, functions, such such as awareness,awareness, awareness,awareness,awareness, awareness, movemen movement, thinking, thinking, thinking, thinking, speech, speech,speech,speech, andand the five senses. senses. senses. xixxixxix,xx CognitionCognition Cognition Cognition - CognitionCognition Cognition Cognition refers refers refers to the mental mental actionactionaction action or process processprocess of acquiringacquiringacquiring acquiring knowledgeknowledge knowledge andand understanding understanding understanding understanding through throughthrough thought, thought, experiences,experiences,experiences, experiences, experiences, experiences,experiences, andand thethe senses.senses. senses. It encompassesencompassesencompassesencompasses encompasses many many aspectsaspects aspectsaspectsaspects of intellectual intellectualintellectual intellectualintellectualintellectual functions functions functions andand proc essesesses such suchsuch as perception, perception, perception,perception,perception, perception, attention,attention, attention,attention, attention, thought, thought, knowledge knowledge formation, formation,formation,formation, formation, memory, memory,memory, working working working memory, memory,memory,memory, judgment judgmentjudgment andand evaluation,evaluation, evaluation, evaluation, reasoning, reasoning,reasoning, reasoning,reasoning,reasoning, andand computation,computation, computation,computation, computation, problem problem-solving solving andand decision decisiondecision decision -making, making, making, comprehension,comprehension, comprehension,comprehension, comprehension, comprehension, andandand language languagelanguagelanguagelanguage production. production.production. production. xxi ,xxiixxiixxiixxii ConcussionConcussion Concussion Concussion - A concussion concussionconcussionconcussion is a typetypetype of TBI TBI caused caused causedcaused by a bump, blow, or jolt to the head headhead or a hit to the body body that causescauses causes the head headhead andand brain brainbrain to movemove move back backback andand forth forth rapidly.rapidly.rapidly. rapidly.rapidly.xxiiixxiiixxiiixxiiixxiii CorpusCorpus CallosumCallosumCallosum Callosum Thinning Thinning - The The corpuscorpus corpus callosumcallosumcallosum callosum is a bundle of nerve nerve nerve fibers fibers in the longitudinal longitudinal longitudinal fissure of the the brai brain that enableenableenableenable correspondingcorresponding corresponding correspondingcorresponding regionsregionsregionsregions of the left left andand right rightright cerebralcerebralcerebralcerebralcerebral cerebralcerebral hemispheres hemispheres hemispheres hemispheres hemispheres to communicate.communicate. communicate. communicate. This cancancan become becomebecome thinned thinned thinned from from repetitive repetitiverepetitiverepetitive repetitive repetitive TBI. TBI. xxivxxivxxivxxiv CerebrospinalCerebrospinalCerebrospinal Cerebrospinal Cerebrospinal FluidFluid Fluid (CSF) (CSF)(CSF) - CSFCSFCSF is the fluid within within the subarachnoid subarachnoid subarachnoidsubarachnoid space, space,space,space, the spinal cord'scord's cord'scord's centralcentralcentral central central canal,canal,canal,canal,canal, andand the brain's brain's brain'sbrain's four ventricles.ventricles.ventricles. ventricles. The fluid is continuouslycontinuously continuously continuously formed formed formed by the choroidchoroid plexus. plexus. xxv CT andand TBI - CT is much more limited limited limited in detecting detecting detecting detecting the widespread widespreadwidespread widespreadwidespread microscopic microscopicmicroscopic microscopic microscopic injury injury injury to axons,axons,axons, leading leading to many many of the long -term term problems problems experiencedexperiencedexperienced experienced experienced experiencedexperienced by TBITBITBI patients.patients.patients. patients.patients. It is not unusual unusual for a CT to be readreadreadread as negativenegativenegativenegativenegative negative in a patient patient patientpatient with a TBI. TBI.xxvi Chronic Chronic Traumatic TraumaticTraumatic Traumatic Encephalopathy EncephalopathyEncephalopathyEncephalopathy Encephalopathy Encephalopathy Encephalopathy (CTE)(CTE) - CTECTE describes describes describesdescribes describes brain brainbrain degeneration degenerationdegenerationdegenerationdegenerationdegenerationdegenerationdegenerationdegeneration likely likely causedcausedcaused caused by repetitiverepetitiverepetitive repetitive repetitive repetitive head headhead trauma. trauma. It is a disorder disorder that is not fully fully understood understood understood andand has has been beenbeen historicall historicall historicallhistoricall y only only diagnosed diagnoseddiagnosed diagnoseddiagnosed at autopsy.autopsy. autopsy.autopsy.xxviixxviixxviixxviixxvii,xxviiixxviiixxviiixxviiixxviiixxviii Diffuse Diffuse Axonal Axonal Axonal InjuryInjury Injury Injury (DAI)(DAI) (DAI)(DAI) - DAI DAI is a form form of traumatictraumatic traumatic brain brainbrain injury. injury. injury.injury. It is a result result of the brain brain shifting shifting rapidly. rapidly. rapidly.rapidly. The long connectingconnecting connectingconnecting connectingconnecting fibers(axons) fibers(axons)fibers(axons) fibers(axons)fibers(axons)fibers(axons) areareare sheared shearedsheared sheared as the brain rapidly rapidly rapidly shifts inside inside the skull. skull. Typically,Typically,Typically, Typically, Typically,Typically, it causescausescauses causescauses injuries injuries injuries to manymany many parts parts of the brain brainbrain andand leaves leaves leaves the patient patient patientpatient comatose.comatose. comatose.xxixxxixxxixxxix Damping Damping Damping ForceForce ForceForce - A dampingdampingdampingdamping force forceforce limits vibrations vibrations vibrations andand is essentialessential in protecting protectingprotecting protecting the the systemsystemsystem in which which it operates. operates.operates.operates. xxx Defenseless Defenseless Defenseless DefenselessDefenseless Position/PlayerPosition/Player Position/Player Position/PlayerPosition/Player Position/PlayerPosition/PlayerPosition/Player - This player playerplayerplayer is extra extra vulnerable vulnerablevulnerable to injury injury injury because becausebecausebecause of their physical physicalphysical physical position position position or focus focusfocusfocus andand concentration.concentration. concentration.concentration. concentration. concentration. concentration. xxxi Dementia Dementia - DementiaDementiaDementia isn't isn't isn't a specific specificspecificspecific disease diseasedisease but a general general generalgeneralgeneral term term for for the impaired impaired impaired impaired abilityability ability ability to think, think, remember remember remember andand makemakemake decisions decisionsdecisions decisions that interfere interfereinterfere interfereinterfereinterfere with daily daily daily activities.activities.activities. activities. activities. xxxiixxxiixxxiixxxiixxxii Depression Depression Depression Depression - Depressionepression epressionepression epression is a mood disorder disorder that that causescausescauses causes persistent persistent persistentpersistent symptomssymptomssymptoms symptoms of feeling feelingfeeling feelingfeeling sad sad or losing losing interest interestinterestinterestinterest in things things thingsthings youyou like. like. like. It affectsaffectsaffects affectsaffects how youyou think, think, feel,feel,feel,feel, andand behave. behave. behave. behave. It can lead leadlead to many many mental mentalmental andand physical physicalphysical physical symptoms.symptoms.symptoms.symptoms. symptoms. 6 Did Not ParticipateParticipateParticipate Participate - The The fact factfact or conditioncondition condition of not being being involved involved involved or participatingparticipatingparticipating participatingparticipating participating participating in something. something. something.xxxiiixxxiiixxxiiixxxiiixxxiiixxxiii Diffusion Diffusion Tensor Tensor ImagingImagingImagingImagingImaging (DTI)(DTI) (DTI)(DTI) - DTI DTI is a refinement refinement refinementrefinement of MRI MRI to see see the unique,unique, directional directionaldirectional directional directional movement movement of molecules,molecules, molecules, molecules, molecules, specifically, specifically,specifically, specifically,specifically, specifically,specifically, water, water, water, alongalong along neuralneuralneural neural tracts. tracts.tracts.tracts. tracts.xxxivxxxivxxxivxxxivxxxiv Evolution Evolution of the NFL NFL helmet helmethelmet - The evolvingevolving evolvingevolving cha changesnges nges to NFL helmets helmets helmetshelmets protect protectprotectprotect players playersplayersplayers better better betterbetter from from TBI.TBI.TBI.TBI.xxxv FluidFluid -based based based biomarkers biomarkersbiomarkersbiomarkersbiomarkersbiomarkers - FluidFluid -based basedbasedbased biomarkers biomarkersbiomarkers biomarkersbiomarkers areareare body body fluidsfluids that that cancancan be tested tested tested andand detect detect detect various various problems. problems.problems. CSFCSFCSF is in direct directdirect contactcontact contact with extracellularextracellularextracellular extracellularextracellularextracellular extracellular fluid, andand its composition composition compositioncomposition composition composition directly directlydirectly directly reflects reflects reflectsreflectsreflects biochemical biochemical biochemicalbiochemicalbiochemical changeschanges changeschanges changes in the brain. brain. Due to this, this, CSFCSFCSF may may be consideredconsidered considered considered considered the optimal optimal source source of biomarkers biomarkersbiomarkersbiomarkers biomarkers for brainbrain brain injury. injury. injury.injury. SomeSome biomarkers biomarkers biomarkers biomarkers in CSFCSFCSF have have alreadyalready alreadyalreadyalready been beenbeen discovered: discovered: discovered: proteins proteins that indicate indicate indicate indicate BBB integrity integrityintegrityintegrity integrity andand neuroinflammation. neuroinflammation. neuroinflammation. neuroinflammation. xxxvi FrontalFrontal Frontal-temporal temporaltemporal Deme Deme ntiantia ntia - This umbrella umbrella umbrella term term describes describes describes describes brain brainbrain disorders disorders affectingaffecting affectingaffectingaffecting affecting the the frontal frontal andand temporal temporaltemporal lobes. lobes. These These areasareasareasareasareas controlcontrol control personality, personality,personality, personality, personality,personality,personality, behavior, behavior, behavior, behavior, andand language. language. language. language. language.xxxviixxxviixxxviixxxviixxxviixxxvii FunctionalFunctional Functional Functional Functional MRI MRI (fMRI) (fMRI) (fMRI)(fMRI) - FunctionalFunctional Functional Functional Functional MRI MRI is a typetypetypetype of MRI MRI that measures measures measuresmeasures brainbrain brain activityactivityactivity activity activity by detecting detectingdetectingdetectingdetecting detectingdetecting changchang changchanges associatedassociated associated associated associated with blood flow. flow. This technique technique relies relies reliesrelies on thethe fact factfact that cerebralcerebralcerebralcerebralcerebral cerebral blood flow andand neuronal neuronal neuronalneuronal activation activation activation activation work work together. together.together.together. together. BloodBlood flow increases increasesincreasesincreases increases to activeactiveactive active areasareasareasareasareas of the the brain. brain. xxxviiixxxviiixxxviiixxxviiixxxviiixxxviiixxxviii Head HeadHead AccelerationAccelerationAccelerationAccelerationAccelerationAccelerationAcceleration Acceleration Acceleration Events EventsEvents (HAE) (HAE) (HAE) - An HAE is a head headhead injury injury injury sustained sustainedsustained from fromfrom th e brain brain moving moving in the skull skull during an impact. impact. impact.impact. It can causecausecause cause a contusion contusion contusion contusion at the impact impact impactimpact site site and opposite opposite the injury. injury. injury.injury.xxxixxxxixxxxixxxxixxxxix Heads HeadsHeads Up FootballFootball - This This is a comprehensivecomprehensive comprehensive comprehensive programprogram programprogramprogramprogram developed developed developed by USA FootballFootball to advanceadvance advance advance player playerplayerplayer safety.safety.safety. safety.safety.safety. HealthHealthHealthHealth Health andand safety safetysafetysafetysafety protocols protocols protocols areare dev developedeloped andand presentedpresented presentedpresentedpresented to players, players,players,players, coaches,coaches, coaches,coaches,coaches,coaches, andand parents. parents. parents. xl Helmet Helmet HelmetHelmet SafetySafetySafety SafetySafety - IncreasingIncreasingIncreasing Increasing IncreasingIncreasingIncreasing safety safety safetysafety measures measures measures measures areare implementedimplemented implementedimplemented implemented in helmets helmets helmetshelmets to try try andand prevent prevent prevent significant significantsignificant significantsignificant brain brainbrain injury. injury. injury.injury.injury.36 Helmets Helmets HelmetsHelmets with sensors sensors - SensorsSensorsSensors areareare embeddedembedded embeddedembedded in a football football player's player'splayer'splayer'splayer'splayer's equipment.equipment. equipment.equipment. The sensors sensors areareare monitored monitored monitored for player playerplayerplayer impact impact impactimpact andand injury injury injury as soon as the player playerplayerplayer steps steps onto the field. field. xlixlixli ImagingImaging ImagingImaging Imaging-based based based biomarkers biomarkersbiomarkers biomarkers - An imaging imagingimagingimaging imaging-based basedbasedbased biomarker biomarkerbiomarker biomarker is a measurement measurementmeasurement measurementmeasurementmeasurement derived derived derived from from one or more more images. images.images.images.images.images. Non -invasive screening screeningscreeningscreeningscreening screening tool. tool.xliixliixliixlii InjuriesInjuries InjuriesInjuriesInjuries leading leadingleading leading to TBI TBI - An injury injury leading leadingleading to a TBITBI is anythinganythinganythinganything anything that that causescausescauses causescauses a bump, blow, or jolt jolt to the brain brain and affectsaffects affectsaffectsaffects how the brainbrain brain works. works. xliiixliiixliiixliiixliii InjuryInjury Injury epidemiologyepidemiology epidemiology epidemiology - ThisThis is a characterizationcharacterization characterization characterizationcharacterization characterization characterizationcharacterization characterization of injury injury injury occurrence,occurrence,occurrence,occurrence, occurrence, occurrence, occurrence,occurrence, the identificationidentification identification identification identificationidentification identification of those risk factors, factors,factors, the strengthstrength strength strength of the effecteffecteffect effecteffect of those risk factors, factors,factors, factors, andand potential potentialpotential potentialpotential protective protective protective protective factors factorsfactors relatedrelatedrelated related to the developmentdevelopmentdevelopmentdevelopmentdevelopment developmentdevelopment andand evaluationevaluation evaluation evaluationevaluation evaluation of injury injury injuryinjury prevention.prevention. prevention. prevention. prevention. 44 Memory Memory Memory - Memory Memory Memory is the the process processprocess used usedused to acquire,acquire,acquire, acquire,acquire, store, store, retain, retain, andand laterlaterlater retrieveretrieveretrieve retrieve information. information. Human Human memory memory memory is the abilityability ability ability to preserve preserve preserve andand recall recallrecallrecall information. information. information. xlivxlivxlivxliv Mild Mild CognitiveCognitive Cognitive Cognitive ImpairmentImpairmentImpairment Impairment (MCI) (MCI)(MCI) - MCI MCI is the stage stagestage between between betweenbetweenbetween the expectedexpectedexpected expectedexpected cognitivecognitive cognitive cognitive decline declinedecline decline of normal normalnormal agingagingaging aging andand the severe severe severesevere andand rapidrapidrapid decline declinedecline decline of dementia. dementia.dementia.dementia. dementia.dementia. CharacterizedCharacterized CharacterizedCharacterizedCharacterizedCharacterized Characterized CharacterizedCharacterized by memory, memory,memory, language, language,language,language,language,language, thinking, thinking, thinking, or judgment judgment problems. problems. 10 Mini Mental Mental StateState Exam ExamExam (MMSE) - The MMSE MMSE is an examexamexamexam for patients patients patientspatients at risk risk of developing developing developing developing dementiadementiadementia andand tracking trackingtracking tracking the progression progressionprogressionprogressionprogression progression of cognitivecognitivecognitivecognitive cognitive decline. decline.decline. decline. decline. The The test is comprisedcomprised of questions questions questions to determine determine determine determine the patient's patient's patient'spatient's patient'spatient's sense sense of self,self,self, awarenessawareness awareness awarenessawarenessawareness of the symptomssymptomssymptoms symptoms they they are experiencing,experiencing,experiencing, experiencing, experiencing, experiencing, experiencing, capabilitycapabilitycapabilitycapabilitycapability capability capability to remember remember remember lists, lists, lists, andand capablecapablecapable capable of following following instructions instructions instructionsinstructions instructions or answeringanswering answering answering simple simple math questions. questions. questions. xlvxlvxlv mTBI mTBI Threshold ThresholdThreshold Threshold - A mTBI mTBImTBI is consideredconsidered considered considered considered a headheadheadhead injuryinjury injury that fallsfallsfalls falls under under a specificspecificspecific specific criterion.criterion. criterion. BrainBrain Brain structures structures structuresstructures areare normal normal on imaging. imaging.imaging.imaging. imaging.imaging. If there there there is a loss of consciousness,consciousness, consciousness,consciousness, consciousness, it lasts less than 30 minutes. minutes. Altered AlteredAltered mentalmental status, feeling feelingfeeling feelingfeeling dazed, dazed,dazed,dazed, confused,confused, confused, or disoriented disorienteddisoriented lasts less than 24 hours. PostPost -traumatic traumatic amnesiaamnesiaamnesia amnesia lasts up to 1 day. day.day.xlvixlvixlvixlvi Medial Medial temporal temporaltemporal lobe - The medial medial temporal temporaltemporal lobe lobelobe is a systsystsyst em of structures structures structures essentialessential for declarative declarativedeclarative declarativedeclarative declarative memory. memory.memory. It consistsconsists consists of the hippocampal hippocampal region regionregion region andand the adjacentadjacent adjacentadjacentadjacent perirhinal, perirhinal, perirhinal, entorhinal,entorhinal, andand parahippocampal parahippocampal parahippocampal parahippocampalparahippocampalparahippocampal regions.regions.regions. regions.xlviixlviixlviixlviixlvii Neuroinflammation Neuroinflammation Neuroinflammation - This This is defined defined defined as an inflammatory inflammatoryinflammatory inflammatory response response within within thethe brain brain or spinal spinal cordcord cord. This This is mediated mediated mediated mediated by the production production production of cytokines,cytokines,cytokines, cytokines, chemokines,chemokines, chemokines, chemokines, reactivereactivereactivereactivereactive oxygen oxygenoxygen oxygen species, species,species, andand secondarysecondarysecondarysecondary secondarysecondary messengers. messengers.messengers.messengers.messengers. xlviiixlviiixlviiixlviiixlviiixlviii Neurological Neurological NeurologicalNeurological Neurological changeschangeschangeschangeschangeschangeschanges - These These areareare changeschangeschangeschangeschangeschangeschanges that affectaffectaffect affectaffect the brain brainbrain andand the centralcentralcentralcentral central andand autonomicautonomic autonomic nervous nervous systems.systems.systems. systems. The symptomssymptomssymptoms symptoms can rangerangerange from from em otional otional otional to physical. physical.physical. physical. xlixxlixxlixxlix NFL SafetySafetySafetySafetySafetySafety ProtocolsProtocols ProtocolsProtocols - NFL safety safety safetysafety protocols protocols areare committedcommitted committed committed to advancingadvancing advancing advancing progress progressprogress in diagnosing, diagnosing, diagnosing,diagnosing,diagnosing, preventing, preventing,preventing, preventing, preventing,preventing,preventing, andand treating treatingtreating treating sports sports -related relatedrelatedrelated injuries, injuries, injuries, enhancingenhancing enhancing enhancing enhancing medical medicalmedicalmedical protocols, protocols, improving improving how the gamegamegamegame is taught taught andand played, played,played,played, andand protecting protectingprotecting protecting the the players' players'players'players' overalloverall overall overall health, health,health, health, safety, safety, safety,safety,safety, andand well well -being. being. being.being.l National National National National FootballFootball LeagueLeagueLeagueLeagueLeagueLeague (NFL) (NFL)(NFL)(NFL) - The The NFLNFLNFL is a professionalprofessional professionalprofessional professional professional football football organization organization organization organizationorganization organization that began began began in 1920 with only only five teams; teams; there there areare nownow 32 teams. teams. li Neurofibrillary Neurofibrillary Neurofibrillary NeurofibrillaryNeurofibrillaryNeurofibrillary tanglestanglestanglestanglestangles (NFT)(NFT) (NFT) - A pathological pathological pathologicalpathologicalpathological pathological accumaccumaccumaccum ulation of paired paired paired helicalhelical filaments filaments composedcomposed composedcomposed of abnormallyabnormally abnormally abnormally abnormally formed formedformed tau protein protein that is found in the cytoplasmcytoplasmcytoplasm cytoplasmcytoplasm of neurons neurons in the brain. brain. liiliilii On field field Neurological Neurological NeurologicalNeurological NeurologicalNeurological ConsultConsult Consult - If an NFLNFLNFL player playerplayerplayer shows anyanyany concussiveconcussive concussive concussive symptoms,symptoms,symptoms,symptoms, symptoms, symptoms,symptoms, they they must be clearedcleared clearedclearedcleared by the team teamteam physici physiciphysici an andand an independent independent independent independent neurological neurological neurologicalneurological neurologicalneurological consultant.consultant. consultant. consultant.consultant. To return return to play, play,play, the player playerplayerplayerplayer must pass passpass the sideline tests from from the independent independent independent neurologicalneurologicalneurological neurologicalneurological neurological consult.consult. consult. liiiliiiliiiliii PreventingPreventing Preventing Preventing Preventing headheadheadhead injuries/TBI injuries/TBI injuries/TBI injuries/TBIinjuries/TBI injuries/TBI - The The NFLNFLNFL has has taken taken many many steps to try try andand make the gamegamegame safer safer safer for athletes.athletes. athletes.athletes. They TheyThey havehavehave banned banned bannedbanned andand penalized penalizedpenalizedpenalized penalizedpenalizedpenalized helmet helmet helmethelmet-to -helmet helmet helmethelmet hits. hits. Kick Kick-off hashashas been beenbeen changedchanged changedchangedchangedchanged to avoidavoid full -speed speedspeedspeed collisions.collisions. collisions. collisions. PracticesPractices PracticesPractices PracticesPracticesPractices areareare reduced reduced reducedreduced contact;contact; contact;contact; the league leagueleague analyzes analyzesanalyzesanalyzes artificialartificial artificial playing playingplaying playing surfaces surfacessurfacessurfacessurfaces to soften soften impacts. impacts. impacts.impacts. livlivliv ProactiveProactive ProactiveProactive Proactive StanceStance Stance - A proactive proactiveproactiveproactive proactive stance stance brings bringsbrings purpose purpose purpose purpose to individual individual andand communal communalcommunal communal work work andand offers offersoffers several several several several benefits. benefits.benefits.benefits. This alsoalso means means trying tryingtrying trying to solve a problem problem as soon soon as you'reyou're you're you're aware.aware. aware.aware.aware.lv Return Return Return-to -play play guidelinesguidelines guidelines guidelines - Every EveryEveryEvery player playerplayerplayer diagnosed diagnoseddiagnosed diagnosed withwith a concussionconcussion concussion must pass pass this 5-step process processprocess to returnreturnreturn to play playplay or practice.practice. practice.practice. practice.practice.practice. PhasePhase Phase 1- symptomsymptomsymptom symptom -limited limited limited activity,activity,activity, activity, activity,activity, PhasePhase Phase 2- aerobicaerobicaerobic exercise,exercise,exercise,exercise, exercise, PhasePhase Phase 3- football football specific specificspecific exercise,exercise,exercise,exercise, exercise, PhasePhase PhasePhase 4- clubclub -basedbasedbased based non -contactcontact contact training training trainingtraining drills, drills, PhasePhase Phase 5- full contactcontact contact drillsdrills andand gameplay. gameplay. gameplay.gameplay.54 SportsSports RelatedRelatedRelated Related ConcussionConcussion Concussion Concussion (SRC) (SRC)(SRC) - An SRCSRCSRC is a TBI fromfrom a direct directdirect or indirect indirect indirectindirect hit with a force forceforce that thatthat travels travels travels to the brain,brain, brain, rapid rapid or slow onset onsetonset of symptomssymptomssymptomssymptoms symptoms symptoms that resolve resolve spontaneously, spontaneously,spontaneously, spontaneously, spontaneously,spontaneously, negative negative negative negative standard standard neuroimaging, neuroimaging, neuroimaging, neuroimaging, neuroimaging,neuroimaging, andand with or without a loss of consciousness.consciousness. consciousness. consciousness.consciousness. lvilvilvi SecondSecondSecondSecond ImpactImpact Impact SyndromeSyndromeSyndrome Syndrome (SIS) (SIS)(SIS)(SIS) - SISSISSIS most common commoncommon ly describes describes describes describes the rapidrapidrapid swelling swelling swelling of the brain brain while a second secondsecond head headhead injury injury injury is sustained sustainedsustained while while recovering recovering recovering recovering recovering fromfrom symptomssymptomssymptoms symptoms from from initial initial initialinitial head headhead trauma. trauma. lviilviilviilvii SportsSports InjuryInjury Injury PreventionPrevention PreventionPreventionPrevention Prevention (SIP) (SIP)(SIP)(SIP) - SIPSIPSIP areare the stepssteps taken taken to reduce reduce reduce the risk of a sports -related related related injury. injury. injury.injury.lviiilviiilviiilviiilviii SubSub -co ncussive ncussive ncussive hits - These TheseThese areareare impacts impacts impactsimpacts below below the the threshold threshold threshold of causingcausingcausing a concussion.concussion. concussion. concussion. The brain brain is shaken shaken shaken but notnot enoughenough enough to causecausecause damage. damage.damage.damage.damage.damage.lixlixlix SusceptibilitySusceptibility SusceptibilitySusceptibility Susceptibility Susceptibility Susceptibility WeightedWeightedWeightedWeightedWeighted ImagesImages Images Images (SWI) (SWI)(SWI) - SWISWISWI is an MRI MRI sequence sequence sequencesequence sequence sensitivesensitivesensitive sensitive to compoundscompounds that distort distort the the local local magnetic magneticmagnetic magnetic magnetic field, field, making it easiereasiereasier to detect detect detectdetect blood products. products. products.lx ,lxilxilxi Tau Tau pathology pathology pathology pathology - Tau pathologypathologypathology pathology pathology accumulatesaccumulatesaccumulatesaccumulates accumulatesaccumulates intracellularly intracellularly intracellularly intracellularly intracellularly intracellularly intracellularlyintracellularly as hyperphosphorylatedhyperphosphorylatedhyperphosphorylated hyperphosphorylated hyperphosphorylated hyperphosphorylatedhyperphosphorylated hyperphosphorylatedhyperphosphorylated tau fibrillates fibrillates fibrillates fibrillates into into paired paired paired helical helical helicalhelicalhelical filaments filaments that form form neurofibrillaryneurofibrillaryneurofibrillary neurofibrillary neurofibrillaryneurofibrillaryneurofibrillary tangle, tangle,tangle,tangle,tangle, ultimately ultimately ultimatelyultimately ultimately killing killing killing the neuron. neuron. 53 TBI BiomarkersBiomarkers BiomarkersBiomarkers Biomarkers - PathophysiologicalPathophysiologicalPathophysiological PathophysiologicalPathophysiologicalPathophysiological PathophysiologicalPathophysiologicalPathophysiological Pathophysiological changeschangeschangeschangeschangeschangeschanges cancancan be seen seenseen on a microscopic microscopicmicroscopic microscopic microscopic level level eveneveneveneven when when they they aren'taren'taren'taren'taren'taren't visible visible on imaging imagingimagingimaging imaging studies. studies.studies. SerumSerumSerum and CSFCSFCSF markers markers markers can be correlatedcorrelated correlatedcorrelatedcorrelatedcorrelated with the severity severity severity severity of the injury injury injury andand cognitivecognitive cognitive cognitive performanceperformanceperformance performance performanceperformance performance andand outcome. outcome. outcome. lxiilxiilxiilxii,37,37,37 Traumatic TraumaticTraumatic Traumatic BrainBrainBrainBrain InjuryInjury InjuryInjury (T BI) BI) - A TBITBI cancancan happen happen happenhappen fromfromfrom many manymany injuries injuries andand be classifiedclassified classified classified by the mechanism mechanismmechanism mechanism of injury, injury,injury,injury,injury, the clinicalclinical clinical clinical severity severityseverityseverity severity as diagnosed diagnosed diagnosed diagnoseddiagnosed by the the Glasgow GlasgowGlasgow ComaComa Scale,Scale,Scale,Scale, or the characterizationcharacterization characterizationcharacterizationcharacterizationcharacterization characterization characterizationcharacterization characterization of structural structural structural damage. damage. damage. damage.27 Traumatic TraumaticTraumatic BrainBrain Brain InjuryInjury InjuryInjuryInjury Threshold ThresholdThreshold Threshold - A head headhead injury injury injuryinjury is consiconsi dered dered dered a TBITBITBI when whenwhen there there is a sudden, sudden, violent violentviolent bump, blow, or jolt jolt to the head. head.head. ThisThis results resultsresults results in loss or decreased decreaseddecreaseddecreaseddecreaseddecreased decreased consciousness, consciousness, consciousness,consciousness, consciousness,consciousness, amnesicamnesic to eventsevents events before before before or afterafter after injury, injury, injury,injury, focal focalfocal neurologicalneurologicalneurological neurological neurological neurological deficits,deficits,deficits, deficits, deficits, andand alterationalteration alterationalteration alteration alteration of mental mental state. state.lxiiilxiiilxiiilxiiilxiii,27,27,27 Three ThreeThree-point stance stancestance - This his is when when the offensive offensiveoffensive offensive lineman lineman lineman has has his feet feetfeet shoulder shoulder shoulder width apartapart apart with one foot slightly slightlyslightly slightly behindbehindbehind the other, other, dropping dropping dropping into into a squatting squatting squatting position position position with the hand hand slightly slightlyslightly slightly inside inside the near nearnear foot in frontfront front of the body. body.body. BodyBody Body weightweightweight weight distribution distribution distribution is 70% body body and 30% 30% hands,ands, other armarm restsrestsrests on the thigh, thigh,thigh, shoulders shoulders shoulders square, square,square, square, andand most importantly, importantly, importantly, importantly,importantly, keepkeepkeepkeep thethe head headhead up to reducereducereduce reduce injury. injury. injury.injury.lxivlxivlxivlxiv Two Two-point stance stance - This is when when a player playerplayerplayer has has feetfeetfeetfeet shoulder shoulder shoulder-width apart,apart, apart, weight weight weight -centered,centered,centered, centered,centered, knees kneesknees bent, bent, andand the only only twotwo things things things touching touching the groungroungroun d areare the player's player'splayer'splayer'splayer'splayer's feet.feet.feet.feet.feet.lxvlxvlxv USA FootballFootball - This This is the governinggoverning governinggoverning governing body body for for amateuramateur amateur American American AmericanAmericanAmerican football. football.football. It'sIt'sIt'sIt's an independent, independent, independent, non -profit profit organization organizationorganization organization that provides provides developmental developmental developmental developmentaldevelopmental andand educationaleducational educationaleducational educational educational tools tools for coachescoaches coachescoachescoachescoaches andand players. players.players.players. lxvilxvilxvilxvi SummarySummarySummarySummarySummary Summary Traumatic TraumaticTraumatic brain brainbrain injuries injuries injuries injuries are the most significant significant significant significantsignificant contributorscontributors contributors to disability disability disability andand death deathdeath worldwide, worldwide, more than anyanyany other traumatictraumatic traumatic injury. injury. injury.injury.64 TBIs TBIsTBIs causecausecause a discrepancy discrepancydiscrepancy discrepancydiscrepancydiscrepancy in normal normal normal brain brain function, function, function, andand anyanyany contactcontact contactcontactcontact injury injury injury to the head headhead puts a person person at risk for a TBI.TBI.TBI.TBI. This kind of injury injury injury does does not discriminate. discriminate. discriminate. discriminate. Every EveryEveryEvery population of people people is at risk for a TBITBITBI post -contactcontact contact head headhead injury. injury. injury.injury.lxviilxviilxviilxviilxvii Excessive ExcessiveExcessiveExcessive Excessive occurrence occurrenceoccurrence occurrenceoccurrence occurrence of TBI TBI cancancan lead lead to a conditioncondition condition called called called chronicchronic chronic traumatic traumatic traumatic encephalopathyencephalopathy encephalopathyencephalopathy encephalopathyencephalopathy encephalopathy (CTE).(CTE). (CTE). CTE amongamong among NFLNFL players playersplayersplayersplayers in the UnitedUnited States StatesStates States has has become becomebecome increasing increasingincreasingincreasingincreasingincreasing ly concerning,concerning, concerning,concerning,concerning,concerning, concerning,concerning, andand with research research researchresearchresearchresearch advances,advances, advances,advances, advances,advances, thethe prevention prevention prevention prevention of CTECTE hashashas been beenbeen exploredexploredexplored explored andand presented presentedpresentedpresentedpresented to the NFL population. The transient transient alterationalteration alterationalterationalterationalteration alteration of brain brain function function function afterafter after exposureexposureexposure to externalexternalexternal external external force forceforce is how the CDCCDC defines defines defines TBI,TBI,TBI,TBI,68 andand this this can be a careercareercareer careercareer-endinendin g injury injuryinjuryinjury for a player playerplayerplayer in the NFL.NFL.NFL.NFL. A TBITBITBI jeopardizesjeopardizesjeopardizes jeopardizes jeopardizesjeopardizes a player's player'splayer'splayer'splayer'splayer's careercareercareercareercareercareer andand cancancan also also impact impact impactimpact their neurological neurological neurologicalneurological neurologicalneurological health healthhealth health for the the rest rest of their life. life. life. This scoping scoping reviewreviewreview of recurrent recurrentrecurrent recurrentrecurrent TBI andand the potential for lifelong lifelong lifelong lifelong consequencesconsequences consequences consequencesconsequences consequencesconsequences in NFL players playersplayersplayers will be used used to raise raise awarenessawareness awareness awareness awarenessawareness regarding regardingregardingregarding regarding the issue issue to anyoneanyoneanyoneanyone interested. interested.interested. interested. Male MaleMale NFLNFLNFL players playersplayersplayers in the United StatesStates States between between betweenbetween 2007 2007 andand 2017 areareare the centercentercenter centercenter of this this review. review. review. We have have systematicallysystematicallysystematically systematicallysystematically systematically systematically mapped mapped literature literature literatureliterature regarding regarding regarding regarding our topic topic by filtering filtering throughthrough through existingexistingexisting existing andand newly newly newly emergiemergi emergiemerging key key concepts,concepts, concepts,concepts, theories, theories, theories, and other sources sourcessourcessources of evidenceevidence evidence to support our research. research. research.research. research. Analytical AnalyticalAnalyticalAnalyticalAnalytical AnalyticalAnalyticalAnalytical searches searchessearchessearchessearches searches of data datadata from from scholarly scholarly scholarlyscholarlyscholarly databases databases werewerewere utilized, utilized, utilized,utilized,utilized, andand the remainder remainder remainderremainder of the included included material material material was accumulatedaccumulatedaccumulatedaccumulated accumulatedaccumulated via medical medical medical records, records,records,records, interviews, interviews,interviews, interviews, autopsyautopsy autopsy reportreportreport s, andand surveys. surveys.surveys. This thesis will include include include subtopicssubtopics subtopicssubtopics like like recognizing recognizingrecognizingrecognizingrecognizing recognizing andand characterizingcharacterizing characterizingcharacterizingcharacterizingcharacterizing characterizing characterizing different differentdifferentdifferentdifferent stages stages of TBI andand typestypestypestypestypes of injuries injuries injuries leading leading to TBITBITBI in conjunctionconjunction conjunctionconjunction conjunction with the prevention prevention prevention prevention andand diagnosis diagnosisdiagnosisdiagnosis diagnosisdiagnosis of TBI. TBI. Also, anyanyany relevant relevant relevantrelevant information information informationinformation information that establishesestablishes establishes establishes a potential link link between between betweenbetween TBI andandand CTECTE andand its impact impact impactimpact on physical physicalphysical physical andandand mental mental health healthhealth health is described described described describeddescribed throughout. The roles roles andand usage usageusageusage of clinicalclinical clinical clinical evaluationevaluation evaluation andand medical medicalmedical imaging imagingimagingimaging imaging will be investigated investigatedinvestigatedinvestigatedinvestigatedinvestigated and reported reported reported reported in this this study. study.study. We hope to conveyconvey convey the importance importance importance importance of fol lowing establishedestablished established established player playerplayerplayerplayer safety safety safetysafety guidelinesguidelines for for contactcontact contact sports like like the NFL. NFL. We alsoalso hope to have have expressedexpressedexpressed expressed the importance importanceimportance importance importance of monitoring monitoring the long -term term effectseffects effectseffectseffects of TBI on NFLNFLNFL players, players,players,players, as thisthis this information information is pertinent pertinent pertinent to the health healthhealth health andand well well -being being of players playersplayersplayers and their friends, friends, families,families,families, families, families,families, andandand colleagues.colleagues. colleagues.colleagues.colleagues.colleagues. colleagues. To implement implement implementimplement real realreal change,change,change,change,change,change,change, there there must must be an evolutionevolution evolution in the mindset mindset andand cultureculture within within the NFL,NFL, NFL, hoping hoping that that any any adoptionadoption of new new rulesrules rules and protocols protocols protocols willwill trickle trickle down to the sub -professionalprofessional professionalprofessional professional professional levels. levels. ChangesChanges ChangesChanges Changes in beh behaviorsaviors areare vital vitalvital forfor the health healthhealth health andand well well -being being being of allall football football players, players,players,players,players, not just those in the NFL. NFL. LiteratureLiterature LiteratureLiterature ReviewReviewReview -Chapter Chapter Chapter 2 Documentation DocumentationDocumentationDocumentationDocumentationDocumentation Documentation The purpose purpose of this this research research researchresearchresearchresearch was was to betterbetterbetter betterbetter understand understand understand traumatic traumatic brainbrain brainbrain injury. injury. injury.injury. Topics Topics consideredconsidered considered considered considered inc luded ludedluded the diagnosis diagnosis diagnosis diagnosisdiagnosis of TBI,TBI,TBI,TBI, long long-term term effects effects effects of TBI,TBI,TBI,TBI, best best treatment treatmenttreatmenttreatment treatmenttreatment options, options, prevention, prevention, prevention, prevention, andand the possible possible link link of TBI to CTE.CTE. The goalgoalgoalgoal with this this study study was was to gain gain a better better betterbetter understanding understanding understanding understanding of TBITBITBI andandand raise raise awarenessawarenessawarenessawareness awarenessawarenessawareness of recurrentrecurrentrecurrentrecurrentrecurrent recurrentrecurrent TBITBITBI andand its potential potential long -te rm effects.effects. effects.effects.effects. An extensiveextensiveextensive review reviewreview of the literature literature literatureliterature literature was was conductedconducted conducted to meet meet these these objectives. objectives. objectives. objectives. The literature literature literatureliterature review review was was limited limited limited to articlesarticles articles using using using specific specificspecific criteriacriteria criteria fromfrom previously previously previously previouslypreviouslypreviously published published published work. work. Articles Articles ArticlesArticles were were reviewed reviewed reviewedreviewed via online online database database database searchessearchessearchessearchessearchessearches searches andand searchsearchsearchsearch searches of reference reference referencereferencereference reference lists. lists. lists. PubMED/MedinePubMED/Medine PubMED/Medine andand Oneseach Oneseach OneseachOneseachOneseach were were first first exploredexploredexplored explored using allall “fields “fields “fields criteria” criteria” criteria” criteria” andand the following keywords: keywords:keywords:keywords: “traumatic “traumatic “traumatic brain brain injury, injury, injury,injury, OR TBI,” TBI,” “Brain “Brain “Brain “Brain injury,” injury,” injury,” injury,” “treatment “treatment “treatment “treatment “treatment “treatment “treatment of TBI,” TBI,” “side “side effecteffect effecteffecteffect OR symptomssymptomssymptoms symptoms of TBI,” TBI,” “Chronic “Chronic “Chronic “Chronic traumatic traumatic traumatic encepencepencepencepencephalopathy,” halopathy,” halopathy,” halopathy,” halopathy,” halopathy,” “OR “CTE,CTE, ” “NFL “NFL “NFL “NFL protocol protocol on helmets,” helmets,” helmets,” helmets,” “ NFLNFLNFL protocol protocol concussion,” concussion,” concussion,” concussion,” “repeated “repeated “repeated “repeated “repeated “repeated “repeated “repeated head headhead trauma trauma in NFLNFLNFL players,” players,” players,” players,” “CTE “CTE “CTE andand TBI,” TBI,” TBI,” TBI,” TBI,” “TBI “TBI “TBI “TBI assessmentassessment assessmentassessment OR diagnosis,” diagnosis,” diagnosis,” “Imaging “Imaging “Imaging “Imaging “Imaging “Imaging of TBI,” TBI,” TBI,” TBI,” ”Imaging ”Imaging ”Imaging ”Imaging ”Imaging ”Imaging ”Imaging of CTE,” CTE,” “prevention “prevention “prevention “prevention “prevention “prevention of TBITBITBI in NFLNFLNFL players,” players,” players,” players,” “ TBITBITBI and NFL,” NFL,” NFL,” “causes “causes “causes “causes “causes of TBI,” TBI,” “TBI “TBI “TBI threshold,” threshold,” threshold,” “NFL “NFL “NFL “NFL helmets” helmets” helmets” helmets” helmets” andand “NFL “NFL “NFL “NFL helmet helmet helmethelmet history”. history”. history”. history”. history”. These These searchsearchsearchsearchsearchsearch criteriacriteria criteria criteria were werewere then appliedapplied appliedapplied to EBSCO EBSCOEBSCOEBSCO host WebWebWeb Databases Databases DatabasesDatabases Databases which which did not result result in the additionaddition addition of anyanyany unique, unique, unique, eligible eligible eligible studies. studies.studies. The search searchsearchsearchsearch intends intendsintends to exploreexploreexplore if in fact factfact a single singlesingle occurrence occurrenceoccurrence occurrenceoccurrence occurrence of, or repeated repeated repeatedrepeated instances instances instancesinstances of TBI alwaysalways alwaysalwaysalways lead leadlead to CTE. And if so, whatwhat what areareare some of the most prevalent prevalentprevalent prevalent prevalent behavioral behavioral behavioral behavioralbehavioral changeschanges changeschanges changes that that might mightmight be observed observed observedobserved in a personpersonperson that had had sustained sustainedsustained a TBI. TBI. How cancancan we predictpredict predict predictpredict who might mightmight be at risk based based based on certaincertaincertain certain factors factorsfactors andand how can we minimize minimize minimize minimize the effectseffects effectseffectseffects of TBITBITBI andand CTECTE for those at the greatestgreatestgreatestgreatestgreatest risk? We alsoalso reviewed reviewed reviewedreviewed publications publicationspublicationspublications publications involving involving human NFL player playerplayerplayer samples samples samplessamples that were were published published published in English English English -language languagelanguage language journals journals journals beginning beginningbeginning beginningbeginning in 2007 andand ending ending 2017. SearchSearchSearchSearch Search termstermsterms similar imilar imilar to those described described described described above,above, above, as well well as population -specific specificspecific modifiersmodifiers modifiers (sport (sport-related,related,related, related, athlete,athlete, athlete,athlete, National National FootballFootball league, league,league, league, CTICTICTI brainbrain brainbrain bank, bank, protective protectiveprotective protective equipment,equipment, equipment,equipment, etc.)etc.) were were alsoalso used used to manually manually manually search searchsearch search Google Google ScholarScholarScholar ScholarScholar for for additionaladditional additional potential articles.articles. articles. Tit Titles andand abstractsabstracts abstractsabstracts of articlesarticles articlesarticlesarticles were werewere screened screenedscreenedscreenedscreened screened to assessassess eligibilityeligibility eligibilityeligibility eligibility eligibilityeligibility for full -text text screening. screening. screening.screening. screening. PrimaryPrimary PrimaryPrimary reasonsreasonsreasonsreasons for exclusionexclusionexclusionexclusion exclusion included: included: included: LocationLocationLocation Location Location outside outside of the United States,States, States, youth/adolescentsyouth/adolescents youth/adolescentsyouth/adolescents youth/adolescentsyouth/adolescents andand females,females,females, females, duplicate duplicate duplicate data, data, did not include NFL, NFL, did not include re petitive petitive petitive petitive TBI,TBI,TBI,TBI, andand outcome not related related related to TBI andand NFL. NFL. Lastly,Lastly,Lastly, Lastly,Lastly, reference reference reference referencereferencereference lists lists from from previously previously previouslypreviously published published published reviewreviewreview reviewreview papers papers papers on TBI TBI andand NFLNFLNFL players playersplayersplayers were werewere specifically specificallyspecifically specificallyspecifically specifically targeted targeted targeted for for hand hand -searching searchingsearching searching searching in additionaddition addition to the reference referencereferencereference referencereferencereference lists lists from from studies studies determined determined determined determined determined eligibleeligible eligibleeligible eligible for our qualitative qualitative qualitative analysis.analysis. analysis.analysis.analysis. analysis. A total totaltotal of 111 articlesarticles met inclusion inclusion criteriacriteria criteria for this this review review review andand of the 111 articlesarticles articles 32 were were specific specificspecificspecific cohortcohort studies studiesstudies of NFL players playersplayersplayersplayers demonstratingdemonstratingdemonstrating demonstrating demonstrating demonstrating changeschangeschangeschangeschangeschangeschanges relatedrelatedrelated related to multiple multiple multiple TBI. TBI. Introduction Introduction Introduction IntroductionIntroductionIntroduction This study study was was designed designed designeddesigneddesigneddesigned to inves tigate tigatetigatetigate the epidemiologyepidemiology epidemiology epidemiology epidemiology andand to raise raise raise awarenessawarenessawarenessawareness awareness awareness of sports related related related brain brainbrain trauma trauma associatedassociated associated with CTECTE andand its subsequent subsequent physical physicalphysical physicalphysicalphysical andand probableprobable probable behavioral behavioralbehavioralbehavioral behavioral changes.changes. changes.changes.changes.changes. The The primary primaryprimary topics topics of discussion discussion or question(s) question(s) question(s) that directed directeddirected our our research research researchresearch research were: were:were:were: How is TBI/CTE TBI/CTE TBI/CTE assessed/diagnosed?assessed/diagnosed? assessed/diagnosed?assessed/diagnosed? assessed/diagnosed?assessed/diagnosed?assessed/diagnosed?assessed/diagnosed? assessed/diagnosed? WhatWhat What typestypestypes types of injuries injuries injuries lead lead to a TBI?TBI?TBI?TBI? Is there there a threshold threshold threshold for for sustaining sustainingsustaining sustaining a TBI?TBI?TBI?TBI? WhatWhat What role, if any,any,any,any, does does medical medicalmedical imaging imagingimagingimaging imaging play? play?play? How to raise raise awarenessawareness awarenessawarenessawareness awareness andand possibly possibly preventpreventpreventpreventpreventprevent TBI? TBI? Assessment Assessment AssessmentAssessment was was mademade basedbasedbased based on key key terms, terms, repetitiverepetitiverepetitive repetitive repetitive repetitive themes themes, andand commoncommon common research research researchresearch research methods. A scoping scoping review review review andand analysisanalysis analysisanalysisanalysis of published published publishedpublished data data waswaswas performed performed performedperformed performed withwith with a focus focus on the specific specificspecific areasareas areasareas mentionedmentionedmentioned mentioned mentioned above. above. The review review was was guided by five processes: processes:processes: (a)(a)(a) identification identificationidentification identification of specific specificspecific researchresearchresearch researchresearch research questions questions questionsquestions andand the domain to be explored,explored,explored, explored, (b) location location location of relevantrelevantrelevant relevant studies, studies,studies, (c) (c) selection selection selection selection of relevant relevantrelevantrelevant relevant studies studies based based based on the predetermined predeterminedpredetermined predetermined predeterminedpredetermined predetermined predetermined inclusion/exclusion inclusion/exclusion inclusion/exclusioninclusion/exclusion inclusion/exclusioninclusion/exclusion criteria,criteria, criteria, criteria, (d) (d) extrapolation,extrapolation,extrapolation, extrapolation, organization, organization,organization, organization,organization, organization, andand analysisanalysis analysisanalysisanalysis of data data fromfrom relevant relevant relevant studies studiesstudies selected, selected, selected,selected, (e) (e) summarization summarizationsummarization summarizationsummarization summarization andand reporting reporting reporting reporting of results.results.results. results. The specific specificspecific specific research researchresearchresearch research questions questionsquestions questions were werewere organized, organized,organized,organized, organized,organized, andand colorcolor codedcoded coded within within a literature literature literatureliterature reviewreviewreview matrix matrix for easeeaseease of future future reference. reference. reference.reference.reference. reference.reference. This scoping scoping reviewreviewreview waswaswas performed performed performed performed to determinedeterminedetermine determine determine if a direct directdirect link link can be establishedestablished establishedestablished established established between between betweenbetween TBITBITBI andand subsequent subsequent subsequent behavio behavio behavio r changeschangeschangeschangeschangeschangeschanges andandand possible possiblepossiblepossible possible CTECTE in former former NFL players. players.players.players. This study study is a synthesissynthesissynthesis of prior prior research research researchresearch research that thatthat will determine determine determine determine how the research research researchresearch research has,has,has, to date, date, driven driven how we study study TBI TBI andand exploreexploreexplore the potential changeschanges changes changeschanges that that may may be associatedassociated associatedassociated associated with repeated repeated repeatedrepeated headheadheadhead injury. injury. injury.injury. The study study surveys surveyssurveyssurveys the need needneed for for more information information to document document the possibility possibility possibility possibility that TBITBITBI may may be responsible responsible responsible for for behaviorbehaviorbehavior behavior changeschangeschangeschangeschangeschangeschanges andand maymaymay be associatedassociated associated with CTECTE in some instances. instances.instances. instances.instances. By clearlyclearly clearly clearly defining defining how how symptomssymptomssymptomssymptoms symptoms sustained sustainedsustained afterafter after eacheacheacheach incidence incidence of TBI TBI areareare related, related, related, the study study will assessassess options options for earlierearlierearlier earlier diagnosis diagnosis diagnosis diagnosisdiagnosis andand measures measuresmeasures measures of prevention. prevention. prevention. prevention. Definition DefinitionDefinition Definition of TBI/CTETBI/CTETBI/CTE TBI/CTE-What What is it? Traumatic TraumaticTraumatic brain brainbrain injuries injuries injuries injuries areare amongamong among the most common commoncommon medical medicalmedical conditionsconditions conditions affectingaffecting affectingaffectingaffecting affecting many,many,many,many,many, with more than one million million million emergencyemergency emergencyemergencyemergencyemergencyemergency room visits visits each yearyearyearyear in the United States.States. States. According AccordingAccording According to the CDC,CDC, TBI is a significant significantsignificant significantsignificantsignificant causecausecause cause of death deathdeath andand disabilitydisability disabilitydisability in the United States.States. States. 60 TBI presents presentspresents presents in various various forms forms ranging rangingrangingranging ranging from from mild alterationsalterations alterationsalterations alterations alterations of consciousnessconsciousness consciousness consciousnessconsciousness to an unrelenting unrelenting unrelenting unrelenting comatose comatose comatose state state andand death. death.death. TBITBITBI cancancan be summarized summarized summarizedsummarized summarizedsummarized as injury injury injury to the brain brain causedcausedcaused causedcaused by sudden sudden impactimpact impact or injury injury injury andand occurs occursoccurs occurs whenwhenwhenwhen a forceforceforceforceforce transmitted transmittedtransmitted transmitted transmitted transmitted to the head headhead causescausescauses causes neuropathologic neuropathologic neuropathologic neuropathologic neuropathologicneuropathologic damage damage damage andand impairment impairment impairment of brain brain function. function. function. TBITBITBI doubles doubles the risk of suicide andand is the major determinant determinant determinant determinant determinant of acquiredacquiredacquired acquiredacquired se izure izure disorders disorders (ASD) (ASD)(ASD) that alsoalso result result from from closedclosed head headhead traumatrauma trauma (CHT) (CHT) significantly significantlysignificantly significantlysignificantly significantly increases increasesincreasesincreasesincreasesincreases the risk of developing developing developing developingdeveloping Alzheimer's Alzheimer's Alzheimer's Alzheimer'sAlzheimer'sAlzheimer's disease disease (AD), (AD),(AD), Parkinson'sParkinson'sParkinson's Parkinson's Parkinson's disease diseasedisease (PD) andand chronicchronic chronic traumatic traumatic traumatic encephalopathyencephalopathy encephalopathyencephalopathy encephalopathyencephalopathy encephalopathy (CTE) ”.lxviiilxviiilxviiilxviiilxviiilxviii It has has long long beenbeenbeenbeen understood understood understood understood that TBI is a severe severesevereseveresevere issue issue that can lead leadlead to long standing health healthhealth health concerns.concerns. concerns.concerns. IndiviIndivi duals duals who experienceexperienceexperience experience experience experience repeated repeated repeatedrepeated TBI areare at an increased increasedincreasedincreasedincreasedincreased risk of developing developingdevelopingdeveloping developing more long -term term issues. issues. issues. ResearchResearchResearch ResearchResearchResearchResearch shows that TBIsTBIsTBIsTBIs can affectaffectaffect affectaffect anyanyany individual individual regardless regardlessregardlessregardless regardlessregardless of ageageage or sex. sex.sex. However, However,However, However, epidemiologicalepidemiological epidemiological epidemiological epidemiologicalepidemiological data data shows that adultadultadult men areare approximatelyapproximately approximately approximately approximatelyapproximately approximately 40% more more likel likel likely to suffer suffersuffer a TBI TBI than adultadult women.women. lxixlxixlxixlxix,1,7,1,7,1,7,1,7 RecentRecentRecentRecentRecent literature literature literatureliterature suggests suggests there there is a multitude multitudemultitude multitude of data data with regards regardsregardsregards to preventing preventingpreventing preventing preventingpreventing TBITBITBI in daily daily daily life. life. life. SafetySafetySafety SafetySafety featuresfeaturesfeaturesfeaturesfeatures features ranging rangingrangingranging ranging fromfrom placing placing placing handrails handrails handrails handrails handrails alongalong along both sides of stairs andand removingremovingremoving removing obstacles obstaclesobstaclesobstaclesobstaclesobstacles from from youryour enviroenviro nment to improvements improvements improvements in safety safety safetysafety equipmentequipment equipmentequipment andand safety safetysafetysafetysafety protocolsprotocols protocols for those at high highhigh risk risk of sustaining sustainingsustaining sustaining a blow to the head, such such as those that play play contactcontact contact sports, sports, areare widely widelywidely availableavailable available availableavailable with a simple simple internet internetinternet internet search. search.search. search. The disruption disruption in brain functionfunction function function due to an externalexternalexternal external external physical physicalphysical physical force force force is the primaryprimary primary primary definitiondefinitiondefinition definition of a TBI. TBI.TBI.2 This can occur occuroccur from from multiple multiple multiple sources sourcessources such suchsuch as penetrating penetrating penetratingpenetrating penetrating penetratingpenetrating objects, objects, rapid rapid movements, movements, andand in particular particular particular of our review,review,review, review, blunt force forceforce trauma trauma trauma in NFL players. players.players.players. WithWith With repetitive repetitive repetitive repetitive repetitive brain brain injuries injuries injuries in these pl ayers,ayers,ayers,ayers, a conditioncondition condition known as CTECTE can occur.occur.occur.occur. 21 CTECTE is a neurodegenerative neurodegenerative neurodegenerative neurodegenerative neurodegenerative neurodegenerative neurodegenerative disease diseasediseasedisease that has has debilitating debilitating debilitating debilitatingdebilitating debilitating effectseffects effectseffectseffects that areare only only identifiable identifiable in postmortem postmortem postmortem brains brains of those studied. studied.studied. 11 There There areare a multitude multitude multitude of signs signssigns andand symptomssymptomssymptoms symptoms ranging rangingrangingranging ranging in severity severity severity severity from from mild to severeevere evere for for TBI TBI’s. Mild Mild physical physicalphysical physical symptomssymptomssymptoms symptoms may may present as dizziness, dizziness,dizziness, headaches, headaches,headaches, headaches,headaches, headaches, nausea/vomiting, nausea/vomiting, nausea/vomiting,nausea/vomiting,nausea/vomiting, nausea/vomiting, nausea/vomiting, nausea/vomiting, andand fatigue. fatigue. fatigue.fatigue. 11 WhileWhile While mild cognitivecognitive cognitive cognitive andand emotionalemotional emotionalemotional emotional issues issues issues such such as concentrationconcentration concentrationconcentrationconcentration concentration concentration problems, problems, anxiety,anxiety, anxiety, anxiety, issues issues issues with short term term memory, memory,memory, irritability irritability irritabilityirritability irritability irritability and trouble falling falling falling falling asleepasleep asleepasleep maymaymay alsoalso occur. occur.occur. lxxlxxlxx,lxxilxxilxxilxxi SymptomsSymptomsSymptoms of CTE cancancan alsoalsoalso vary varyvary andand include include manymany many of the symptomssymptomssymptoms of a mildmild TBI. TBI. However, However, However, However, these symptomssymptomssymptoms symptoms can be more serious serious andand eveneven even life life threatening. threatening.threatening.threatening. threatening. threatening. Mild Mild symptoms,symptoms,symptoms, symptoms, like like that of TBI, TBI, but alsoalso include include include dizziness, dizziness,dizziness, slurred slurred speech, speech,speech,speech, confusion, onfusion, andand ringing ringing ringing ringing in the ear.ear.ear. 5 Extreme Extreme Extreme symptomssymptomssymptoms symptoms areare consideredconsidered considered considered considered to be seizures, seizures, seizures, seizures, loss of consciousness,consciousness, consciousness, consciousness,consciousness, impulse impulse control,control, aggression,aggression, aggression, aggression, andand paranoia.paranoia.paranoia. paranoia. lxxiilxxiilxxiilxxiilxxii,55,55,55 TBI is prevalent prevalentprevalent prevalent acrossacrossacross across the nation nation nation within within allall demographics. demographics. demographics. demographics. demographics.demographics. However, However,However, However, some populations areare more suscepti susceptisusceptisuscepti ble to TBI TBI than others. others. NFL football football players playersplayersplayers areare the most vulnerable vulnerablevulnerable to TBI.TBI.TBI.TBI. We aimedaimed aimedaimed to extrapolateextrapolateextrapolate extrapolate extrapolateextrapolate andand assessassess assessassess the broad broad definition definition definition of TBI, TBI, signs signs & symptoms,symptoms,symptoms, symptoms, andand treatmenttreatment treatment treatment methods. In the latter portion of the paper, paper,paper,paper,paper, NFL TBITBITBI-related related related statistics statistics statisticsstatistics areare present presentpresentpresent ed.ed. Injuries Injuries Injuries that lead to TBI.TBI.TBI. Is there therethere a threshold thresholdthreshold threshold for sustainingsustainingsustainingsustaining sustaining sustaining TBI?TBI?TBI? WhatWhat What injuries injuries injuries lead lead to TBI? Is there there a threshold threshold threshold for for sustaining sustainingsustaining sustaining a TBI?TBI?TBI?TBI? These These areare very veryvery important important important questions, questions, questions, andand in an attemptattempt attemptattempt to answeranswer answer andand fully fully understand understand understand specific specificspecificspecific injury injury injury protocols,protocols, protocols, what what methods best best formulate formulate formulate prevention prevention prevention prevention andand protectionprotection protectionprotection protection measures measures measures againstagainst against TBI, TBI, a scopingscoping scopingscoping review review review of scholarly, scholarly, scholarly,scholarly,scholarly, peer peerpeer-reviewed reviewed reviewedreviewed journals journals was was performedperformedperformed performed performedperformed to help help gaingaingain clarityclarity clarity clarity to those questions. questions. questions. questions. questions. Numerous Numerous studies studiesstudies have have beenbeen been conductedconducted conductedconducted andand werewerewere reviewedreviewedreviewed reviewedreviewed to investigate investigateinvestigateinvestigate what hat injuries injuries injuries injuries causecausecause TBI andand at what what threshold, threshold,threshold, threshold, if any.any.any.any. InjuriesInjuries Injuries leading leadingleading to TBI TBI cancancan be readilyreadilyreadilyreadily readily categorizedcategorizedcategorized categorizedcategorized categorizedcategorized andand identified. identified. The threshold threshold threshold of exactlyexactlyexactlyexactlyexactly exactly when whenwhen a TBITBITBI takes takes takes place, place,place, most likely likely likelylikely due due to the infinite infinite geneticgeneticgeneticgeneticgenetic genetic andand physical physicalphysical physicalphysical factors, factors,factors, is much more difficult difficult difficult to propose. propose. propose. Experimental Experimental Experimental Experimental models of TBI have havehave significantly significantlysignificantly significantlysignificantly significantly advancedadvancedadvanced advanced advancedadvanced our understanding understanding understanding understanding understanding of pathophysiology pathophysiology pathophysiologypathophysiology pathophysiologypathophysiologypathophysiology leading leading leading to secondary secondarysecondary secondarysecondary brainbrain brain injury injury injury andand have have led to the developmentdevelopmentdevelopment developmentdevelopment of many many potential neuroprotective neuroprotective neuroprotective neuroprotectiveneuroprotective neuroprotective agents.agents. agents. However, However,However,However,However, fewfewfew of these neuroprotective neuroprotective neuroprotective neuroprotective neuroprotective strateg strategstrateg strategies have have beenbeenbeenbeen translated translated translated into into improved improved improved clinical clinical carecarecarecare for patientspatientspatients patientspatients with acuteacuteacute head headhead trauma trauma andand other brain brain injuries. injuries. Several SeveralSeveralSeveral factorsfactorsfactorsfactors factors may may contributecontribute contribute to the limited limited success successsuccesssuccess of clinicalclinical clinicalclinicalclinical translation, translation,translation, translation, but one key key factor factorfactor is likely likely likelylikely the lack lack of correspondencecorrespondence correspondencecorrespondence correspondence correspondence betwee betwee betweebetween current current experimentalexperimentalexperimental experimental experimental models and the conditionsconditions conditions experiencedexperiencedexperienced experienced experienced experiencedexperienced in real realreal-life life accidents.accidents.accidents.accidents. Generally, Generally, Generally,Generally,Generally, Generally,Generally, (especially (especially (especially(especially (especially in reference reference reference reference reference to our study study of NFL TBITBITBI cases)cases)cases) cases) TBITBITBI is grouped groupedgrouped under under closedclosed head headhead injury. injury. injury.injury. ClosedClosed Closed head headhead injuries injuries injuries occur occuroccur when whenwhen there there there is a sudden suddensudden jolt, jolt, bump, or blow to the head. head.head. PenetratingPenetratingPenetrating Penetrating PenetratingPenetrating Penetrating injury injury injury (injury(injury (injury (injury(injury that penetrates penetratespenetratespenetrates penetrates the skull) skull) is anotheranother subcategory subcategorysubcategory subcategory subcategory of TBI TBI but will not be focused focused focused on due due to lack of relationrelationrelation to TBI with with relation relation relation to the NFL. NFL. TheThe risk of developing developingdevelopingdeveloping developing CTE,CTE, with relation relation to American American AmericanAmerican football, football,football, football, inc reases reasesreasesreasesreases with the number of yearsyearsyearsyears participating participating participating participating in the sport. In a groupgroup of 111 veteranveteran veteran NFLNFLNFL players, players,players,players, 110 were were diagnosed diagnoseddiagnosed diagnoseddiagnosed with CTECTE andand displayed displayeddisplayeddisplayeddisplayed “extensiveextensiveextensive brain brain atrophatroph y, astrogliosisastrogliosis astrogliosis astrogliosis , myelinatedmyelinatedmyelinatedmyelinated myelinated myelinated axonopathyaxonopathyaxonopathy axonopathy axonopathy, microvascular microvascularmicrovascular microvascularmicrovascularmicrovascular injury, injury, injury,injury, perivascular perivascular perivascularperivascularperivascular neuroinflammation neuroinflammation neuroinflammation , andand phosphorylated phosphorylated phosphorylated phosphorylated phosphorylatedphosphorylated phosphorylated tau protein proteinprotein pathology pathology pathology pathology”.69 BasedBasedBased Based on this this studystudy studystudy alone,alone, NFL players playersplayersplayers areareare highly highlyhighly highly susceptiblesusceptible susceptiblesusceptible susceptible to TBI. TBI. WithWith With relationrelationrelation to the NFL, NFL, the majoritymajoritymajority majority of TBITBITBI injuries injuries injuriesinjuries occur occuroccur with anotheranother another helmeted helmeted helmetedhelmeted player. player.player.player. Although AlthoughAlthough elbows,elbows, elbows, knees, knees,knees, andand the ground ground can alsoalso be causescausescauses causes of TBI in the NFL, NFL, surveys surveys surveyssurveys show helmet helmet helmethelmet-to -helmet helmet helmethelmet co ntact ntact as producing producingproducing the the vast vast number of reported reported reported TBITBITBI incidents. incidents.incidents. Thresholds ThresholdsThresholds Thresholds for sustaining sustainingsustaining sustainingsustaining a TBI areareare difficult difficult to quantify quantify quantifyquantify or predict.predict. predict. A biomechanical biomechanicalbiomechanicalbiomechanical biomechanical biomechanical study study of human concussionconcussion concussion concussion attemptsattempts attemptsattempts attempts to relate relate mechanical mechanical mechanical mechanical input to localized localized localizedlocalizedlocalized tissue tissue deformation, deformation, deformation, such such as pres pressure, sure,sure, stress/strain stress/strain stress/strain stress/strain stress/strain responses, responses, is needed neededneeded needed for a proper properproper assessmentassessment assessmentassessment assessmentassessment of brain brain injury injury injury outcome. outcome. A specified specifiedspecified specifiedspecified insult insult known to interrupt interruptinterrupt interrupt brain brain function function should should be quantified, quantified,quantified, quantified, quantified, at least least in principle. principle. principle.principle. In other words, words, there there must be a threshold thresholdthreshold threshold below below which which no loss of fun ctionction ction occurs occursoccurs andand a ceilingceilingceiling ceiling beyondbeyondbeyondbeyond which which irreversible irreversibleirreversible irreversible changeschangeschangeschangeschangeschangeschanges in brain brainbrain function function function would occur. occur.occur. SuchSuch Such information information informationinformation information is crucialcrucial crucial when whenwhen human tolerance tolerancetolerancetolerancetolerance tolerance datadatadata areareare used used to design design designdesign protective protectiveprotective protective systems.systems.systems. There There is no question question question that computercomputer computercomputer models capablecapablecapablecapablecapable of simulating simulating impact impact impactimpact events events events can be of major major assistanceassistance assistanceassistance assistance to researchersresearchersresearchers researchersresearchersresearchersresearchers researchersresearchers in the study study of brainbrainbrainbrain injuries. injuries. injuries. BrainBrainBrainBrain tissue tissue is naturally naturally naturallynaturally naturally inhomogeneous inhomogeneous inhomogeneousinhomogeneous inhomogeneous andand anisotropicanisotropic anisotropic andand such such material material material definitions definitions definitions should should be incorporated incorporated incorporated into into a brain brainbrain model to obtain a more realisticrealisticrealisticrealistic realistic realistic injury injury injury response.response.response. Re cently, cently, cently,cently,cently, severalseveralseveral severalseveralseveral possible possible injury injury injury predictorspredictors predictors predictors based based based on head headhead response response variablesvariables variables variables have havehave been beenbeen suggested suggested using finite -elementelement element (FE) (FE) headheadheadhead models. RuanRuan Ruan et al.al. andand ZhouZhou et al.al. indicated indicatedindicatedindicated that shear shearshear stress/strain stress/strainstress/strain stress/strain stress/strain response response couldcould be the injury injury injury indicator indicatorindicatorindicator for subarachnoid subarachnoidsubarachnoidsubarachnoidsubarachnoid he matoma matoma andand diffuse diffuse axonalaxonalaxonal axonal injury injury injury (DAI). (DAI).(DAI).(DAI).(DAI). BandakBandakBandak Bandak andand EppingerEppinger EppingerEppinger suggested suggested suggested that an accumulatedaccumulatedaccumulatedaccumulated accumulatedaccumulated volume volume of those elementselements elements exceedingexceedingexceedingexceedingexceedingexceeding exceeding a predetermined predeterminedpredetermined predetermined predetermined predetermined maximum maximum maximum principal principal strain, strain, referred referredreferredreferred referredreferred to as the CumulativeCumulative Cumulative Cumulative Cumulative StrainStrain Strain Damage Damage Damage MeasureMeasure MeasureMeasure Measure (CSDM), (CSDM), (CSDM), was was related related related to strain strain -induced induced DAI. DAI.DAI. Al -BsharatBsharat BsharatBsharat Bsharat et al.al. modified modified modified the model model developed developed by ZhouZhou et al.al.al. to simulatesimulate simulate simulate large large relative relative motion motion between between betweenbetween thethe brain brain andand the skull skull andandand implied implied implied that relative relative motion motion can play play a role in brain brain injury. injury. injury.injury. However, However,However, However, none of the aboveaboveabove studies studiesstudies utilized utilized utilizedutilizedutilized data andand in jury jury from from actualactualactual actualactual field field incidents incidents to predict predict injury. injury. injury.injury. The midbrain midbrain midbrainmidbrain was was found to be the probableprobable probable anatomicalanatomicalanatomicalanatomical anatomical anatomical substratum substratum substratum of concussion.concussion. concussion. concussion. This areaarea area alsoalso provided provided thethe strongest strongest correlationcorrelation correlation correlation with MTBI MTBI occurrence. occurrence.occurrence. occurrence.occurrence. occurrence.occurrence. Translational TranslationalTranslational andand rotational rotational rotational rotational accelerationaccelerationaccelerationaccelerationacceleration accelerationacceleration acceleration were were found to be essentialessential elementselements elements for an injury injury injury to occur. occur.occur. Clinical Clinical diagnosis,diagnosis, diagnosis,diagnosis, diagnosis, the roles of imaging imaging imaging modalitiesmodalities modalities modalities modalitiesmodalities in recognitionrecognitionrecognitionrecognition recognition of signs signs and and symptoms symptomssymptoms symptomssymptoms of TBI ConcussionConcussion Concussion Concussion andand TBI TBI areare often often used used interchangeably, interchangeably,interchangeably, interchangeably,interchangeably,interchangeably,interchangeably,interchangeably,interchangeably,interchangeably,interchangeably,interchangeably,interchangeably, when when in fact factfact they they areare not alwaysalways alwaysalways synonymous.synonymous.synonymous. synonymous.synonymous. synonymous. This scienti scienti fic confusionconfusion is reflected reflected reflectedreflected by the factfactfactfact that TBITBITBI hashashas been beenbeen defined defined more than 40 different differentdifferentdifferentdifferent ways waysways in the scientific scientific literature. literature. literature.literature. literature.literature.7 TBI has has beenbeenbeenbeen classifiedclassified classified as mild, mild, moderate, moderate,moderate, andand severe severe severe basedbasedbased based on the combinationcombination combination combination combination of clinicalclinical clinical clinical features featuresfeatures featuresfeaturesfeatures and results results results of imaging imagingimagingimaging imaging testing. testing. CurrentlyCurrently CurrentlyCurrently Currently the GlasgowGlasgow Glasgow GlasgowGlasgow Coma Scale Scale (GCS)(GCS)(GCS) (GCS) andand Post Traumatic TraumaticTraumatic Traumatic AmnesiaAmnesia Amnesia (PTA)(PTA) clinicalclinical clinicalclinicalclinical tests tests areareare being being being used usedused in determining determining determining determining the severityseverityseverity severity severity of symptomssymptomssymptoms symptoms in patients patients patientspatients andand aidingaiding aiding in the diagnosis diagnosisdiagnosisdiagnosis diagnosis of TBI/concussion. TBI/concussion.TBI/concussion. TBI/concussion. TBI/concussion.TBI/concussion. TBI/concussion. Evolution Evolution of clinicalclinical clinical clinical diagnosis andand management managementmanagementmanagement hashashas mademade substantial substantialsubstantial substantialsubstantial gainsgainsgains with the development development development developmentdevelopment of the GCS and the PTAPTA scale. scale.scale. These TheseThese tools provide a grading grading grading scalescalescalescale based basedbasedbased solely solely on the clinicalclinical clinical clinical presentation presentation presentation presentationpresentation presentation of the patient patient patientpatient andand symptoms.symptoms.symptoms. symptoms.symptoms. Grades GradesGrades Grades cancancan be betterbetterbetter betterbetter defined defined defined alongalong along a spectrum spectrumspectrum when when assignedassigned assignedassignedassignedassigned a numerical numerical numerical value,value,value, thus allowingallowing allowing the severity severity severity severity to be more definitively definitively definitively definitivelydefinitively assessed.assessed. assessed. This scale scalescale is only only basedbased on these three three assessments:assessments: assessments: motor motor responsiveness, responsiveness, responsiveness, responsiveness, responsiveness, verbal verbal verbal performance, performance, performance, performance,performance,performance,performance, andand eyeeyeeye opening openingopening to appropriateappropriate appropriate appropriate stimuli. stimuli.stimuli. stimuli. According AccordingAccording According to the CentersCentersCentersCenters Centers for Disease DiseaseDisease ControlControl (CDC), the GC S was designed designed designeddesigned designed andand should should be used used to evaluateevaluate evaluate evaluate the depthdepthdepth and duration duration duration of a comacoma and/orand/or impaired impaired impairedimpaired impaired consciousnessconsciousness consciousnessconsciousness consciousnessconsciousness consciousness only only by a qualifiedqualified qualified qualified qualified physician. physician.physician. physician.physician. Also, the scale scalescale cancancan help help gaugegaugegaugegauge the impact impact impactimpact of a wide wide variety variety varietyvariety of conditionsconditions conditions such such as acuteacuteacute acute brain brain damagedamagedamage damage due to traumati traumati c and/orand/or vascular vascular vascular vascular injuries injuries injuries or infections, infections,infections, infections, metabolic metabolic metabolic disorders disorders disorders (e.g.,(e.g.,(e.g.,(e.g.,(e.g., hepatic hepatic hepatic hepatic or renalrenalrenal renal failure, failure, failure, failure, hypoglycemia,hypoglycemia,hypoglycemia, hypoglycemia,hypoglycemia,hypoglycemia,hypoglycemia,hypoglycemia,hypoglycemia, hypoglycemia,hypoglycemia, diabetic diabetic diabetic ketosis),ketosis), ketosis), ketosis), etc.etc. lxxiiilxxiiilxxiiilxxiiilxxiiilxxiii,17,7,17,7,17,7,17,7,17,7 Other Other contextualcontextual contextual symptomssymptomssymptoms symptoms such such as perceived perceived perceived cognitivecognitive cognitive cognitive impairments, impairments, impairments, impairments, photophobia,photophobia, photophobia,photophobia, phonophobia andand behavioral/ behavioral/ behavioral/ behavioral/behavioral/ emotionalemotional emotional changeschanges changeschangeschangeschanges that might mightmight be observed observed observed by the the patient patient patientpatientpatient or family family familyfamily can alsoalso aidaid the the diagnosis. diagnosis.diagnosis.diagnosis. diagnosis.diagnosis. diagnosis. Duration DurationDuration Duration of PTAPTA usually usually usually correlatescorrelates correlatescorrelatescorrelatescorrelates well well with GCS andand usually usually usually lasts aboutabout fourfour times times longer longerlonger than thanthan unconsciousness. unconsciousness. unconsciousness. unconsciousness.unconsciousness. lxxivlxxivlxxivlxxivlxxiv,lxxvlxxvlxxvlxxv,1,17,1,17,1,17,1,17,1,17 ConcussionsConcussions Concussions Concussions areare classified classified classified based based based on the criteriacriteria criteria set by these rating rating ratingrating scales. scales.scales.scales.scales. TheyThey They incorporated incorporated incorporated objective, objective,objective,objective, objective, objective, measurable measurable measurable valuesvaluesvalues that previously previouslypreviously previouslypreviously werewerewere ill -defined defined defined such such as the level level of consciousnessconsciousness consciousness consciousnessconsciousness (LOC)(LOC)(LOC) at the time of injury, injury, injury,injury, causecausecause of injury injury injuryinjury andand duration duration duration of PTA.PTA. PTA. PTAPTA can be defined defined defined as the time afterafter after a period period of unconsciousness unconsciousnessunconsciousness unconsciousness unconsciousnessunconsciousness when when the injured injured injured personpersonperson person is conscious conscious conscious andand awakeawakeawakeawake but is behaving behavingbehavingbehaving or talking talking in a bizarre bizarrebizarrebizarrebizarre or uncharacteristic uncharacteristicuncharacteristic uncharacteristicuncha