Concussion Research Update…Why Our Patients Need OMT

AAO Convocation March 13-17, 2019

P. Gunnar Brolinson, DO, FAOASM, FAAFP, FACOFP Discipline Chair, Sports Medicine Director, Primary Care Sports Med Fellowship Team Physician, Virginia Tech Team Physician, US Ski Team Funding and Disclaimer

DOT: National Highway Traffic Safety Administration American Osteopathic Association 1051715717 National Science Foundation Toyota Central Research and Development Labs, Inc NIH: R01HD048638 NIH: 1R01NS094410-01A1 NCAA-DoD Care Consortium

I do not have any relevant financial relationships to be discussed, directly or indirectly, referred to or illustrated with or without recognition within this presentation. Concussion evaluation, treatment and research is a “team game”! • Stefan Duma • Mark Rogers • Mike Goforth • Lauren Leslie • Brett Griesemer • Natalie Hyppolite • Rick Greenwald • Al Kozar • Jonathan Beckwith • Shawn Kerger • Joel Stitzel • Peter Fino • Steve Rowson • Murray Nussbaum • Bethany Rowson • Erik Tahkounts • Jillian Urban • Gerry Gioa • Chris Whitlow • And there are many others…. • Logan Miller Introduction • The human brain possesses functional complexity far beyond that of any other organ or body part • When injured, it is this complexity that creates tremendous clinical challenges for both diagnosis and treatment • Recognizing concussion and differentiating it from other diagnoses can be a daunting task, but one of critical clinical importance • Understanding the intersection between research and clinical care • Returning the athlete to play safely is of fundamental importance for the clinician • Understanding the role of Equipment, Rules Changes, Coaching and other “countermeasures” is vitally important No health topic in recent memory has captured the public’s attention as much as the debate on sports related traumatic brain injury.

The deal calls for the NFL to pay $765 million to fund medical exams, concussion-related compensation, medical research for retired NFL players and their families, and litigation expenses, according to a court document filed in U.S. District Court in Philadelphia. So what have we learned…. Concussions misunderstood and feared by most Americans

Sponsor UPMC, 10/05/2015

The national survey of 2,012 Americans age 18 and over was conducted in April by Harris Poll on behalf of UPMC. The survey further showed that, despite a lack of knowledge and understanding, there is a high level of concern and even fear across the country.

A fear of concussions may be impacting parents’ decisions to let their kids play contact sports

This survey was conducted online within the United States by Harris Poll on behalf of UPMC between April 16 to 23, 2015 among 2,012 U.S. adults age 18 or older, 948 of whom are parents. For complete survey methodology, including weighting variables, please contact Deana Percassi, Harris Poll, 585-214-7212. “Concussion”…the movie

• Concussion is an American sports drama film directed and written by Peter Landesman, based on the 2009 GQ article Game Brain by Jeanne Marie Laskas. The film stars Will Smith, Alec Baldwin, Gugu Mbatha- Raw and Albert Brooks. The film focuses on a forensic pathologist and neuropathologist, Dr. Bennet Omalu played by Smith, who discovers Chronic Traumatic Encephalopathy (CTE) in the brains of two NFL players. • Principal photography began on October 27, 2014, in Pittsburgh, Pennsylvania. Village Roadshow Pictures, Scott Free Productionsand The Shuman Company are producing the film. Columbia Pictures will release the film as scheduled for an opening December 25, 2015 date. What is a Concussion?

• Concussion is defined as a complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces • Several common features that incorporate clinical, pathologic and biomechanical injury constructs that may be utilized in defining the nature of a concussive head injury include: – 1. Concussion may be caused either by a direct blow to the head, face, neck or elsewhere on the body with an impulsive force transmitted to the head – 2. Concussion typically results in the rapid onset of short lived impairment of neurologic function that resolves spontaneously, however in some cases symptoms may evolve over minutes to hours – 3. Concussion may result in neuropathological changes, but the acute clinical symptoms largely reflect a functional disturbance rather than a structural injury – 4. Concussion results in a range of clinical signs and symptoms that may or may not involve loss of consciousness. Resolution of the clinical and cognitive symptoms typically follows a sequential course; however, it is important to note that, in a small percentage of cases, post-concussive symptoms may be prolonged – 5. No abnormality on standard structural neuroimaging studies is seen in concussion

Consensus Statement on Concussion in Sport; 5th International Conference on Concussion in Sport McCrory, P, et al. Br J Sports Med 2017; 0: 1-10 doi:10.1136/bjsports 2017-097699 Incidence of Concussion • 1.6 to 3.8 million traumatic brain injuries/year – 300,000 sport-related concussions • Concussions represent an estimated: – Up to 9% of all high school athletic injuries – 3-6% of interscholastic football athletes – 4-8% of collegiate athletes – 7.7% of National Football League (NFL) athletes • 53% of concussed high school athletes go unreported Langlois JA,Rutland-BrownW,WaldMM.The epidemiology and impact of traumatic brain injury: a brief overview.

McCrea et al, 2004 J head Trauma Rehabil. 2006; 21:375–378. What is a concussion?

• Not all athletes have the same threshold for concussion – But every athlete, whether previously concussed or not, walks on to the field of play with some inherent risk of being concussed • If different athletes receive the same type and magnitude of mechanical force applied to their brains, some will be concussed while others will not • Athlete’s past concussion experience, concurrent diagnoses, physiologic state, and family history may play roles

“Yep, I’m flying through the air, this is not good” Ricky Bobby Current Research and Clinical Considerations for Concussed Athletes Must be managed in on individualized basis and multiple factors taken into account.

For this talk we will synthesize research findings and clinical practice into an integrated approach….

“The current literature is unclear and contradictory regarding specific therapeutic approaches. Sports clinicians are left to develop an approach to management of concussion that is based on currently available best practices that have little scientific evidence to support them.”

P.G. Brolinson; management of sport related concussion review and commentary; Clin J Sport Med Journal Club issue 24(1) -Jan 2014. Concussion Biomechanics

• Heading a soccer ball can result in head accelerations – From 16 to 20g lasting 25 ms • The average collegiate football impact – From 21 and 32g lasting 14-15 ms • Impacts to the top of the head yielded the greatest linear acceleration and impact force magnitude – Improper tackling techniques • Offensive and Defensive line players sustained the lowest-magnitude impacts but the highest number of impacts during games and practices

Rowson, S et al. Presented at Rocky Mountain Bioengineering Symposium & International ISA Biomedical Sciences Instrumentation Symposium 17-19 April 2009, Milwaukee, Wisconsin, www.isa.org Halsted, M and K Walter. Pediatrics, 2010; 126 (3): 597-615 Broglio, SP, et al. Journal of Athletic Training 2009;44(4):342–349 Concussion Biomechanics

• Over 250,000 head impacts recorded at Virginia Tech – Games (30%) – Practice (70%) – 15 years of data collection: 2003- 2018

• Clinically diagnosed concussive impacts recorded for instrumented players

• Unbiased exposure data – Previous football work over-sampled injury data Example MTBI Event Example MTBI Event

Peak G = 136 G

Clinically diagnosed concussion Another Example MTBI Event Another Example MTBI Event

Peak G = 139 G

Clinically diagnosed concussion Concussion Biomechanics and Brain Modeling • Appreciate computational models • Brain deformation varies widely by impact of the brain and their potential to location (or direction of motion) and even counterintuitively compared to impact study impact exposure magnitudes • Observe variations in response of • Important implications for quantifying the brain under different loading concussion risk and long term exposure to directions and severities concussive and subconcussive impacts • Investigators using imaging to identify • Understand value and necessity of potential biomarkers for injury predictive of brain models to connect sensor long-term outcomes based exposure with imaging and • Imaging includes advanced structural clinical outcomes techniques to evaluate brain microstructure and advanced functional techniques (fMRI, • Sensor-driven biomechanical MEG) and molecular imaging like PET modeling holds the key to • Imaging is limited now because target of pinpointing areas in brain at most TBI in brain is elusive due to injury risk from TBI or impact exposure. heterogeneity Brain Finite Element Models

ABM SIMon GHBMC SUFEHM

Miller et al. (2016)Takhounts et al. (2003) Mao et al. (2013) Sahoo et al. (2014) THUMS 4.01 KTH WHIM UCDBTM

Kimpara et al. (2006) Kleiven et al. (2002) Ji et al. (2014) Horgan and Gilchrist (2004) Brain Motion... And Sulcal strains (Ghajari, 2017)

http://www.cap.org/ The promise of modeling….

Head Injury Criteria typically relate: linear and rotational kinematics (motion) to injury risk

. 1 퐻퐼퐶 = 푎 푡 푑푡 푡 −푡 푡 −푡

휔 휔 휔 퐵푟퐼퐶 = + + 휔 휔 휔 Prob. of Injury of Prob.

HIC/BrIC

But: Kinematic based measures are arguably Poor discriminators of TBI risk… Modeling shows the possible explanation why Need Metrics that Better Discriminate Loads

• Maximum Principal Strain (MPS) • Strain Rate • Volumetric Strain • Strain Energy • Von Mises Stress • Shear Stress • Intracranial Pressure (ICP)

Introduce and demonstrate the Atlas Brain Model to evaluate brain response for routine youth football head impacts Example 2: 83 g, 9922 rad/s2

1 00 x y 5 0 z resultant 0

-50 Linear AccelerationLinear (g) -100 0 1 0 2 0 3 0 4 0 Tim e (m s)

4 ) x 1 0 2 1 x y 0 .5 z resultant 0

-0.5

-1

Angular Acceleration(rad/s Angular 0 1 0 2 0 3 0 4 0 Tim e (m s) SIMon says: CSDM predicts 14% probability of concussion The ABM (Miller, 2016)

• Atlas-based brain model (ABM)1 developed from the geometry of the ICBM brain atlas brain CSF ventricles • Brain material properties 1Miller et al. (2016) determined through multi- objective optimization • Validated against localized brain motion in 5 cadaver impact experiments

falx skull tentorium

International Consortium for Brain Mapping (ICBM) Brain Atlas Data Collection

• Data from 3 youth teams – 9-12 years of age – 2012-2015 seasons • 119 athletes • 40,538 impacts Example Youth Football Impact Impact Locations

• Impacts corresponding to six (6) impact locations were identified – Locations adapted from Rowson et al. (2011) and

Beckwith et al. (2012) 1 ~40 g ~70 g

0.9 Impact # HITS 0.8 Location Impacts 0.7 A A 4084 0.6 B C 0.5 D B 1450 CDF 0.4 E C 222 F 0.3

D 158 0.2 E 193 0.1

0 F 599 0 20 40 60 80 100 120 140 Linear Acceleration (g) 70 g’s Frontal Impact (Loc. A)

70 g’s

2 Displacement (mm) Displacement 1

0 0 10 20 30 40 Time (ms) 40 g’s Lateral Impact (Location D)

40 g’s

2 Displacement (mm) Displacement 1

0 0 10 20 30 Time (ms) Diagnosing Concussion

• Diagnostic challenge is the fact that every concussion is unique • Difficult to establish a single ‘‘gold standard’’ test for concussion – Some signs and symptoms of concussion may not be present immediately, but may evolve over several hours to days after a concussive episode • Concussion remains a clinical diagnosis based on a constellation of signs and symptoms and requires a high index of suspicion

Kutcher, J.S. and J.T. Eckner. Curr. Sports Med. Rep.,2010; 9(1): 8-15

Consensus Statement on Concussion in Sport; 5th International Conference on Concussion in Sport McCrory, P, et al. Br J Sports Med 2017; 0: 1-10 doi:10.1136/bjsports 2017-097699 Diagnosing Concussion • If an athlete shows concussion-like signs and reports symptoms after a contact to the head he or she should be removed from the practice or competition and be evaluated. Consensus Statement on Concussion in Sport; 5th International Conference on Concussion in Sport McCrory, P, et al. Br J Sports Med 2017; 0: 1-10 doi:10.1136/bjsports 2017-097699

Halsted, M and K Walter. Pediatrics, 2010; 126 (3): 597-615. Guskiewicz, K.M. et al. J of Ath Train 2004; Diagnosing Concussion

• Student-athletes suspected by their coach, athletic trainer, or team physician of sustaining a concussion or brain injury in a practice or game shall be removed from the activity at that time • A student-athlete who has been removed from play, evaluated, and suspected to have a concussion or brain injury shall not return to play that same day nor until • (i) evaluated by an appropriate licensed health care provider as determined by the Board of Education and • (ii) in receipt of written clearance to return to play from such licensed health care provider VHSL legislation. 2010 Standardized Assessment of Concussion • Any decrease from the baseline score on a SAC found to be 95% sensitive and 76% specific for a concussion

Halsted, M and K Walter. Pediatrics, 2010; 126 (3): 597-615 McCrory, P, et al. Clin J Sport Med 2009;19:185–200 Balance Error Scoring System (BESS)

McCrory, P, et al. Clin J Sport Med 2009;19:185–200 Cognitive Rest • Athletes with concussion often have difficulty – Attending school – Focusing on schoolwork and taking tests – Especially in math, science, and foreign-language classes – Reading, even for leisure, commonly worsens symptoms • Rest may include – A temporary leave of absence from school – Shortening of the athlete’s school day – Reduction of workloads in school – Allowance of more time for the athlete to complete assignments or take tests • Other activities that require concentration and attention, including playing video games, using a computer, and viewing television, should also be discouraged

A Review of Return to Play Issues and Sports-Related Concussion Doolan, Brolinson, et al Annals of Biomedical Engineering, Vol. 40, No. 1, January 2012 pp. 106–113 Return To Learn Protocol

• Progression but gradually increasing cognitive demands – Increasing amount of time in school – Increasing the nature and amount of work, length of time spend on work, and difficulty of work – If symptoms do not worsen, demands may continue to gradually increase – If symptoms do worsen, activity should be stopped and student allowed to rest • Student-athlete shall progress to where he/she no longer needs academic modifications/support

PRIOR TO FULL return to Consensus Statement on Concussion in Sport; 5th competition International Conference on Concussion in Sport McCrory, P, et al. Br J Sports Med 2017; 0: 1-10 doi:10.1136/bjsports 2017-097699 Physical Rest

• Broad restrictions of physical activity should be recommended – Including the sport or activity that resulted in the concussion – Any weight training – Cardiovascular training – Physical education classes

A Review of Return to Play Issues and Sports-Related Concussion Doolan, Brolinson, et al Annals of Biomedical Engineering, Vol. 40, No. 1, January 2012 pp. 106–113 Return To Play

• Return-to-play decisions must be made with the risks of possible symptom exacerbation and prolongation of recovery, subsequent concussion, or catastrophic injury in mind

A Review of Return to Play Issues and Sports-Related Concussion Doolan, Brolinson, et al Annals of Biomedical Engineering, Vol. 40, No. 1, January McCrory, P, et al. Clin J Sport Med 2009;19:185–200 2012 pp. 106–113 Neuropsychological Testing

• ANAM (Automated Neuropsychological Assessment Metrics) • CogState • HeadMinder • ImPACT • Pencil-and-paper testing • King-Devick Test

http://impacttest.com/ Legislating Risk

• Texas (2007), Washington (2009) and Oregon(2009) passed the first concussion-specific laws covering scholastic sports • Since 2009 50 Sates and DC have enacted youth sports TBI laws aimed at increasing awareness or reducing risk of repeat injury or both. • These laws represent a uniform but not scientifically proven consensus about the minimum time a young athlete should refrain from reentering contact sports activities. • Also exhibit divergence regarding the health care professional best qualified to make the RTP decision. • Existing youth TBI laws are not designed to reduce initial TBIs. Continued research and evaluation of existing laws will be needed to develop a more comprehensive risk reduction program.

Schwartz, A. The New York Times; 9/13/10 United States Government Accountability Office, Testimony Before the Committee on Education and Labor, House of Representatives; 5/20/10

Harvey, H; American Journal of Public Health: May 16, 2013 See Montgomery County Public Schools Concussion Updated Spring Policy for more details 2015 NCAA

• “Institutions shall have a concussion management plan on file such that a student-athlete who exhibits signs, symptoms or behaviors consistent with a concussion shall be removed from practice or competition and evaluated by an athletics healthcare provider with experience in the evaluation and management of concussion. Student-athletes diagnosed with a concussion shall not return to activity for the remainder of that day. Medical clearance shall be determined by the team physician or their designee according to the concussion management plan. • In addition, student-athletes must sign a statement in which they accept the responsibility for reporting their injuries and illnesses to the institutional medical staff, including signs and symptoms of concussions. During the review and signing process student-athletes should be presented with educational material on concussions.” -- NCAA Memorandum April, 2010 www.ncaa.org/health-safety The brain is the only organ without a blood test

Thyroid Tests MuscleTests • TSH • Aldolase • Free T4 • ANA • Free T3 • Creatine • Total T3 Kinase • Thyroid • ESR Antibodies Calcitonin Cardiac Tests • Thyroglobulin • Troponin • CK-MB • Myoglobin Lung Tests • BNP • Procalcitonin • NT-proBNP • Surfactant proteins • hs-CRP • Copeptin Pancreatic Tests • Amylase • Lipase Adrenal Gland • Trypsin • Adrenomedullin

Renal Tests • Glucose Liver Tests • BUN (Blood Urea Nitrogen) • Alanine aminotransferase (ALT) • CreatinineBUN/Creatinine • Alkaline phosphatase (ALP) Ratio • Aspartate aminotransferase (AST) • Estimated Glomerular Filtration • Bilirubin Rate (eGFR). • Albumin • Calcium • Total protein (TP) • Sodium, Potassium, Chloride, • Gamma-glutamyl transferase (GGT) Carbon Dioxide, Total • Lactate dehydrogenase (LDH) • Albumin • Prothrombin time (PT) • Phosphorus What’s the latest news??? Banyan Biomarker Panel for TBI GFAP UCH-L1

GFAP dimer

Glial Fibrillary Acidic Protein Ubiquitin Carboxyl-Terminal Esterase L1

• Structural protein of the • Small compact 24 kDa protein intermediate filament of Astroglia 50 • Expressed at a high level in neurons kDa • 5% of total brain protein • Highly enriched in the nervous system. • 1% of total brain protein The Glymphatic System

Virchow-Robin Space and Interstitial Flow • production of CSF is not only derived from the choroid plexus but also from water flux dynamics occurring at the Virchow-Robin space (VRS) • CSF interstitial flow directly drains into lymphatic channels at the base of the skull, suggesting a pathway that is equivalent to a drainage system for the clearance of waste molecules from the brain • hydrodynamic process is bidirectional in terms of communication flux and is driven, in part, by respiratory and cardiac pressure pulsations The Glymphatic System OMT and the Glymphatic System

OMT applied to the glymphatic system would have the same 4 goals as OMT applied to the lymphatic system: ① open myofascial transition areas ② maximize diaphragmatic movement ③ augment lymphatic flow, and ④ mobilize fluid in the lymphatic- venous system

The Glymphatic-Lymphatic Continuum: Opportunities for OMM. McCrory P, et al. JAOA March 2016 | Vol 116 | No. 3 Osteopathic Concepts and Concussion Acute head trauma can create temporary craniosacral SD • Direct input forces are linear and rotational or can be “impulsive” transmitted from elsewhere in the body SD in head trauma can occur in any part of the neurocranium, viscerocranium or sacrum • Multiple dural attachments: from cranium through spinal canal into sacrum

Diagnosis is made by ART: Screen, Scan, Segmental Diagnosis • Observation of Asymmetry • Palpation for position • Palpation for mobility and tissue texture of areas involved Where do I look for somatic dysfunction? Somatic Injury: think flexion-extension type dysfunctions: • Impaired cranio-cervical flexion (OA) • Impaired lower cervical extension, mid to upper thoracic extension • 1st/2nd rib elevations • Lumbosacral compression What is autonomic innervation head ? • Sympathetic: T-L outflow T1-4, Infer & Super Cerv ganglia • Parasympathetic: 4 Ganglia: Ciliary, Pterygopalatine, Otic, & Submandibular What is somatic innervation of head ? • Somatic motor fibers of cervical nerves innervate muscles derived from cervical somites including the prevertebral (ventral rami) and postvertebral (dorsal rami) muscles, and the strap muscles (ansa cervicalis) • The cervical spinal nerve plexus formed by the ventral rami of C2, 3 & 4, innervates the anterior and lateral skin of the neck and innervate the posterior scalp and neck What is lymphatic drainage of head ? • Newly determined Glymphatic pathways What is arterial/venous flow to head ? • Why might they be vulnerable to SD ? What was direction/mechanism of impact ? • For direct cranial membranous, sutural, &/or intra-osseous restrictions • Compression of SBS is common, esp in football HEAD IMPACT BIOMECHANICS, THE CLINICAL DIAGNOSIS OF SPORT RELATED CONCUSSION AND THE APPLICATION OF OSTEOPATHIC STRUCTURAL DIAGNOSIS & TREATMENT BROLINSON, LESLIE, ROGERS, KOZAR, GRIESEMER, VCOM Prospective, Longitudinal, Observational Cohort Design – AOA Research Grant • 3 subject groups • Cohort 1: Concussed athletes • Cohort 2: “High Impact” (>98g) athletes • Previous research has demonstrated that this is the linear head acceleration threshold for increased risk of concussion • Cohort 3: Non-concussed non-impact athletes • Recruitment Goals: • Men & Women, multiple sports HEAD IMPACT BIOMECHANICS, THE CLINICAL DIAGNOSIS OF SPORT RELATED CONCUSSION AND THE APPLICATION OF OSTEOPATHIC STRUCTURAL DIAGNOSIS & TREATMENT BROLINSON, LESLIE, ROGERS, KOZAR, GRIESEMER, VCOM

• Specific Aim 1: Conduct a prospective, longitudinal, multi-sport investigation that delineates the typical osteopathic findings in concussion in both men and women by incorporating a multi-dimensional assessment of standardized clinical measures of post concussive symptomatology, Neuro EEG parameters, performance-based testing and psychological health including osteopathic structural diagnosis. • Specific Aim 2: Correlate head and neck impact biomechanics with osteopathic structural evaluation through instrumenting collegiate football players with helmet-mounted accelerometer arrays. A regression model will be developed from controlled laboratory impact tests to relate head acceleration measurements on the field to neck loads and moments experienced by athletes during play. Comparisons will be performed within a contact athlete cohort and between contact and non-contact cohorts. HEAD IMPACT BIOMECHANICS, THE CLINICAL DIAGNOSIS OF SPORT RELATED CONCUSSION AND THE APPLICATION OF OSTEOPATHIC STRUCTURAL DIAGNOSIS & TREATMENT BROLINSON, LESLIE, ROGERS, KOZAR, GRIESEMER, VCOM Methods • Full OMT evaluation and treatment for each subject • OMT (+) regions recorded • OMT is specific to individual HEAD IMPACT BIOMECHANICS, THE CLINICAL DIAGNOSIS OF SPORT RELATED CONCUSSION AND THE APPLICATION OF OSTEOPATHIC STRUCTURAL DIAGNOSIS & TREATMENT BROLINSON, LESLIE, ROGERS, KOZAR, GRIESEMER, VCOM Methods • Neuro EEG performed before and after OMT evaluation and treatment for each subject Balance Error Scoring System (BESS)

• An assessment of postural stability • Performed with the subject in 3 positions – Standing flat on both feet with hands placed on the iliac crests – Standing on a single leg on the nondominant foot – Standing flat on both feet with eyes closed • First on a firm surface and then on a 10-cm- thick piece of foam • the Balance Error Scoring System (BESS) and other commonly used clinical balance tests, suffer from moderate to poor reliability and provide little information about the neuromuscular control system.

McCrory, P, et al. Clin J Sport Med 2009;19:185–200 Decreased high-frequency center-of- pressure complexity in recently concussed asymptomatic athletes • Balance assessments are an integral part of concussion assessments to ensure athletes with previously disrupted balance are fit to return-to-play • Compared with traditional clinical balance measures, nonlinear dynamic analysis of postural stability has shown greater sensitivity in identifying postural control differences post-concussion • One example of nonlinear dynamic balance control is the complexity of postural control calculated by applying entropy algorithms to center-of-pressure (COP) time-series What did we do?

• We evaluated the postural control complexity of recently concussed and healthy athletes and physically active non- athletes to identify and interpret postural control abnormalities that are present 1–6 weeks post- concussion. What did we do?

• 2 minutes, eyes closed, barefoot quiet • The same equipment and quiet standing standing on the force plate task was used with healthy non-athlete • Center-of-pressure (COP) recorded with participants. Four different quiet standing force platform at 1000 Hz conditions were recorded. • Concussed athletes tested at weekly – Normal = “Stand still for two minutes” interval for 6 weeks – Co-Contraction = “Contract all your leg muscles as hard as possible while • Control athletes tested once standing still” – Cognitive = “Silently count down from 800 by sevens while standing still” – Random = “Randomly control your body sway” What did we find out?

• Three complexity measures detected differences between concussed and control athletes at least once • Each significant difference indicated less complexity in recently concussed athletes. • The Co-Contraction condition produced significantly greater complexity in low frequency ApEn, SampEn, and high frequency MVCompMSE Discussion

• These results present the first direct evidence of postural complexity deficits during the sub-acute time frame (1-6 weeks) post-concussion – Results agree with previous studies that reported acute and persistent deficits in postural complexity. • Concussion impacts the complexity of high frequency COP oscillations – decreased COP complexity post-concussion may be due to increased co-contraction or stiffened musculature as an adaptation to decreased balance control • Decreased high frequency complexity post-concussion may be associated with decreased passive muscle stiffness. – may be caused by decreased co-contraction, less stiff lower extremity musculature, and/or potentially more cortical inhibition/less excitability to initiate corrective ballistic corrective contractions. Fino PC, Nussbaum MA, Brolinson PG. Decreased high-frequency center-of-pressure complexity in recently concussed asymptomatic athletes. Gait Posture. 2016 Oct;50:69-74. PMID: 27580081 Cavanaugh JT, et al Sports Med 35, 935-950, 2005

De Beaumont L, et al. J Athl Train 46, 234-240, 2011 Concussion and Gait

• Gait abnormalities and delayed reaction times exist following concussion and can persist for up to 2 months3,4

Concussed – DT

Concussed - ST

Control

• Increased frequency of any injury (including another head injury) after concussion for up to one year5

3Howell et al. (2013) Arch Phys Med Rehabil ; 4Powers et al. (2014) Gait & Posture; 5Nordström et al. (2014) BJSM What did we do?

• Eight NCAA Division I varsity athletes (four concussed, four matched controls participated in this longitudinal study. • No concussed athlete had a prior concussion. • For each concussed athlete, a control participant was recruited from teammates of the concussed subject and was individually matched based on sport, position, skill level, and stature Turning Strategies Concussion and Motor Control

• Growing evidence that mild traumatic brain injury (concussion) affects locomotor characteristics for prolonged periods of time even when physical signs and symptoms are absent • This study longitudinally examined kinematic characteristics during preplanned turning in a small sample of recently concussed athletes • Concussed athletes had larger dual- task costs in turning speed and stride time compared to healthy controls. • Concussion alters the motor control strategy during complex maneuvers

Fino PC, Nussbaum MA, Brolinson PG. Decreased high-frequency center-of-pressure complexity in recently concussed asymptomatic athletes. Gait Posture. 2016 Oct;50:69-74. PMID: 27580081. Fino, Nussbaum, Brolinson Journal of NeuroEngineering and Rehabilitation (2016) 13:65 DOI 10.1186/s12984-016-0177-y Concussion and Motor Control

• Concussed athletes exhibiting greater segmental reorientation variability and less COM clearance around obstacles during turns • Decreased interhemispheric brain connectivity has been reported following concussions which may limit the available cortical resources and the ability of recently concussed athletes to process multiple demands • Navigational and DT gait differences are concerning considering the large cognitive loads and high degree of mobility required in most sports • athletes, who typically have enhanced navigational skills may have altered neuromuscular performance that persists after return-to-play Concussion and Lower Extremity Injury Risk

• Growing evidence suggests that concussion increases the risk of lower extremity (LE) musculoskeletal injury • A retrospective study examined medical records from 110 concussed athletes and 110 matched controls for LE injuries in the 365 days before and after the concussion event • Concussion was associated with an increased instantaneous relative risk of LE injury when adjusting for LE injury history – The incidence of acute lower extremity (LE) injuries, in particular, is 2.48 to 3.39 times more likely in concussed athletes compared with controls in the 90 days after a concussion

Effects of Recent Concussion and Injury History on Instantaneous Relative Risk of Lower Extremity Injury in Division I Collegiate Athletes Aug 2017 Clinical Journal of Sport Medicine Fino, Becker, Fino, Goforth, Brolinson Motion in Running…the neuromuscular system at work Post Concussion Syndrome • A function of the length of symptom persistence – 3 months duration of 3 or more symptoms • Of retired NFL players who were diagnosed with post-concussion related depression, 87% continued to have lifelong symptoms • Medications that address symptoms may be considered in the treatment of PCS – Dosing should begin low and Jotwani, V et al. Curr. Sports Med. Rep.; 2010; 9 (1): 21-26 titrated upward slowly Halsted, M and K Walter. Pediatrics, 2010; 126 (3): 597-615 Summary of Gunnar’s clinical treatment Pearls for PCS

• Remember that dx and tx is a “team event” • For depression with diffuse “body pain” – Psychologists, neurologists, PM&R, PT’s – Effexor and Cymbalta (SNRI’s) and ATC’s can all be involved – Tricyclics • Don’t forget to evaluate the HPA axis for – SSRI’s don’t seem to work well endocrine dysfunction • For “fogginess” • You are treating “symptoms” – Omega 3 supplements – Antioxidants • For mild insomnia with head/neck pain • Alpha Lipoic Acid 100mg QD – Flexeril 10mg at hs • B Complex – Elavil 10-25mg at hs • Co Q 10 100-200mg QD – Trazodone 50-75mg at hs – Amantadine • For headache • 100-200mg BID • Remember to include physical therapy and – NSAIDs neurocognitive rehab as appropriate – Topamax 25-50mg BID • In general avoid narcotics and – OMT benzodiazepines • “autonomic rebalancing”

Placebo-Controlled Trial of Amantadine for Severe Traumatic Brain Injury; Gianco et al; N Engl J Med 2012; 366:819-826March 1, 2012DOI: 10.1056/NEJMoa1102609 Migraine Headaches

• It is possible that migraine headache is a risk factor for concussion • It also is possible that concussion leads to the development of migraine headaches – Or that migraine headaches are being misdiagnosed as concussions • Athletes with migraines may have more severe and prolonged concussion courses after injury

Kutcher, J.S. and J.T. Eckner. Curr. Sports Med. Rep.,2010; 9(1): 16-20 Clinical Considerations for Athletes with Multiple Concussions • To date, no specific number of concussions has been established to mandate season ending injury or retirement. • Experts understand that repetitive concussions can be associated with significant and prolonged neurocognitive deficits – decreased time between concussions – increased recovery time – concussions resulting from decreased biomechanical forces • Clinicians may wish to consider a full neuropsychological evaluation and the use of advanced diagnostics and imaging techniques in these athletes.

A Review of Return to Play Issues and Sports-Related Concussion Doolan, Brolinson, et al Annals of Biomedical Engineering, Vol. 40, No. 1, January 2012 pp. 106–113 Clinical Considerations for Athletes with Multiple Concussions • When to remove an athlete from the competitive season or recommend permanent retirement from competition? – Must be managed in on individualized basis and multiple factors taken into account – Utilize the sports medicine team and appropriate diagnostic modalities • “One opinion is no opinion”

P.G. Brolinson; management of sport related concussion review and commentary; Clin J Sport Med Journal Club issue 24(1) -Jan 2014. Clinical Considerations for Athletes with Multiple Concussions Remove for Season Career Ending • Prolonged post concussive • Pathologic abnormality such as Chiari symptoms malformation • Intracranial hemorrhage • 3 “simple” concussions in a • Clinically relevant imaging abnormality single season • Diminished academic performance or • 2 or more “complex” cognitive abilities concussions in a single season • Persistent prolonged post-concussion syndrome • decreased academic and • Decreased threshold for concussion athletic performance • 3 or more “complex” concussions during • clinically relevant imaging career abnormality. • Persistent neuropsychiatic symptoms A Review of Return to Play Issues and Sports-Related Concussion Doolan, Brolinson, et al Annals of Biomedical Engineering, Vol. 40, No. 1, January 2012 pp. 106–113 What about repetitive “sub concussive” impacts?

• Millions of individuals have played contact sports for many years without obvious functionally significant adverse effects, and without developing progressive neurodegenerative disorders.

• Nevertheless, we are concerned that repetitive head impacts may have an adverse effect on some athletes. – It is reasonable to speculate that individual differences such as polymorphisms in

genes modulating response to neurotrauma39 (e.g., APOE, BDNF, ANKK1) or other host factors may play a role – it is tempting to hypothesize that risk of chronic traumatic encephalopathy or other long term effects of contact sports may represent a gene–environment interaction between repetitive mild neurotrauma and genetic vulnerability to heightened injury response or attenuated neural repair.

McAllister TW, Flashman LA, Maerlender AC, Greenwald RM, Beckwith JG, Tosteson TD, Crisco JJ, Brolinson PG, Duma SM, Duhaime AC, Grove MR and Turco JH. “Cognitive Effects of One Season of Head Impacts in a Cohort of Collegiate Contact Sport”. Neuro. 2012 May 29;78(22):1777-84. What is Chronic Traumatic Encephalopathy???

• A progressive neurodegenerative syndrome • Dementia Pugilistica… – “Punch Drunk Syndrome” • Accumulation of Tau Protein in neurologic tissue – Genetically determined? – Head trauma triggered? – “Over-production” vs “Inadequate Clearance”? • Presents clinically after a prolonged latent period • A composite syndrome of mood disorders – associated neuropshychiatric and cognitive impairments • Definitive diagnosis is by direct tissue analysis post mortem Brain tissue from 18-year-old multi-sport athlete

BU Center for the Study of Traumatic Encephalopathy History of CTE

First described by Harrison Martland (NJ coroner) in 1928 as a change in mental state in boxers, “Punch Drunk Syndrome” CTE in Football

1937 Columbia Daily Spectator

Awareness of long-term consequences of head trauma in football as early as late 1800s, back of photo reads “Navy football team in which cadet Reeves wore first helmet—1894 CTE in Football • Real controversy began in 2005 when Bennet Omalu, MD published “Chronic traumatic encephalopathy in a National Football League player” in Neurosurgery • Described a case of CTE in a former NFL player (Mike Webster) who died of a heart attack • Brain looked normal grossly, but he decided to look microscopically because of his history of mental illness NFL MTBI committee members (Casson, Pellman, Viano) requested retraction of Omalu’s paper CTE in Football

The authors refused to retract CTE in Football

Omalu published a second paper on CTE in former NFL player Terry Long The “Concussion Crisis” and Chronic Traumatic Encephalopathy • In a convenience sample of 202 deceased players of American football from a brain donation program, CTE was neuropathologically diagnosed in 177 players across all levels of play (87%), including 110 of 111 former National Football League players (99%). • In a convenience sample of deceased players of American football, a high proportion showed pathological evidence of CTE, suggesting that CTE may be related to prior participation in football.

JAMA. 2017;318(4):360-370. doi:10.1001/jama.2017.8334 The “Concussion Crisis” and Chronic Traumatic Encephalopathy

• What are the potential issues with this study? – ascertainment bias associated with participation in this brain donation program • public awareness of a possible link between repetitive head trauma and CTE may have motivated players and their families with symptoms and signs of brain injury to participate in this research – the VA-BU-CLF brain bank is not representative of the overall population of former players of American football – this study lacked a comparison group that is representative of all individuals exposed to American football at the college or professional level “Concussion Crisis” and CTE

• Not entirely clear if CTE is unique to traumatic brain injury – CTE-like pathology has also been seen in the brains of people who’ve died with epilepsy, without any history of head trauma. – cases of opioid overdose deaths where the brains show signs of early aging, including tau accumulation • Replication and independent verification are two crucial steps in the scientific process – Many of the health issues attributed to CTE haven’t passed these tests Medical Legal Issues…

• In the months before his suicide in 2012, former NFL linebacker Junior Seau didn't receive proper care from his doctor, David Chao (former Chargers team physician), according to a case filed against Chao • The board said Chao, 52, failed to exercise proper caution in the extended use of Ambien with a patient showing signs of depression and suicidal thought. During the last 18 months of Seau’s life, the board said Chao wrote him 14 prescriptions for Ambien, a sleep drug associated with increased incidence of impaired driving and suicide. • The former San Diego Chargers team doctor was placed on probation for four years and will not be allowed to prescribe the drug Ambien during that time Concussion “Crisis” and mental health issues… • Suicide risk… – cohort of 3439 NFL players with at least 5 credited playing seasons between 1959 and 1988 – Standardized mortality ratios (SMRs), the ratio of observed deaths to expected deaths, and 95% CIs were computed for the cohort – standardized rate ratios were calculated to compare mortality results between players stratified into speed and non-speed position types. – Suicide among this cohort of professional football players was significantly less than would be expected in comparison with the United States population • There were no significant differences in suicide mortality between speed and nonspeed position player

Suicide Mortality Among Retired National Football League Players Who Played 5 or More Seasons; AJSM; May 2016; Lehman, Heinz and Gersic For the persistently symptomatic concussion patient that has NOT been osteopathically evaluated and treated… • Poor Neuromuscular Control and Kinetic Chain Dysfunction • Abnormal muscle firing sequences on muscle testing • Poor proprioception and balance (esp w eyes closed) • Need for frequent Manual Medicine • “Weak” phasic muscles on exam • Easy fatigability of phasic muscles • Chronic pain • Postural decline • Symptoms of tendinopathy • Poor “core” strength Principles of OMT/Sequencing the Exercise Prescription/Neuromuscular Retraining

• Normalization of segmental function and motion through manual medicine • Sensorimotor balance retraining • Comprehensive, symmetric, flexibility – Stretch to symmetry then go for overall increase in length • Re-educate movement patterns - PRECISION – Normalize firing patterns – slow, precise, minimalist movements – Quality of movement (neuromotor control) over quantity – Start unloaded, progressive load, sports specific movements • Strengthening • Sport Specific Conditioning Thoughts on Rules Changes, Technique and “The Game” • "There's still the warrior mentality of the players, which we can relate to," Carroll said. "But through proper education and awareness, the way they play is shifting. It's clear our game is not the same as it was, but it's still OK. It's fine. • "And guys like [Seahawks safety] Kam Chancellor can be as physical and tough as anybody in football and still make the right decisions on hitting guys to keep the game safe. I would have never thought I would be saying this; I see the game different now." Journal of Neurosurgery 2014 • Riddell Revolution helmet reduces risk of concussion by 53.9% compared to VSR4

• Consistent with STAR Ratings, which predict 54.2% risk reduction

• Data compiled from 8 collegiate football teams: Concussion Incidence Minimization

• Reduce exposure to head 3 Strategies: impact • Rule changes and enforcement • Proper technique Rule Proper • Improved diagnostic Changes Technique capabilities Most Effective +

• Reduce concussion risk for remaining head impacts Better Equipment • Improve helmet design

Fewest Concussions Summary

• Data suggest that female athletes may have a higher incidence of concussion and experience more severe concussive symptoms • We are just now beginning to research and understand risk and clinical implications for concussion in youth sports • The presence of preexisting mood or learning disorders can confound pre-injury baseline testing as well as concussion diagnosis and management • Multiple concussions are associated with increased risk of: – Mood disorders (anxiety and depression) – Cognitive dysfunction • Migraine headache and concussion have similar presentations – Athletes who have migraines also may be at a higher risk of being concussed but not know if this is a “cause and effect” relationship • The genetics of concussion remain a mystery, and the role of factors such as the ApoE promoter gene are being investigated • Brain Biomarkers and Advanced Imaging Technologies are an emerging area of research for enhancing our clinical diagnostic capability, The FDA has recently approved the first blood test. • There are some data to suggest that concussion risk may increase as an athlete fatigues or if he or she continues to participate in the sport after sustaining an initial mild traumatic injury • Regarding helmets…more padding is more better! We choose to do these things, “not because they are easy, but because they are hard, because that goal will serve to organize and measure the best of our energies and skills, because that challenge is one that we are willing to accept, one we are unwilling to postpone, and one which we intend to win.”

John F. Kennedy