A Comprehensive Model for Assessment and Management of Mild TBI in the Emergency Department

Future Directions in TBI Research: Leveraging Sports Concussion Research Toward a Neurobiopsychosocial Model

Michael McCrea, PhD, ABPP

Professor of Neurosurgery and NeurologyDirector of Brain Injury ResearchMedical College of WisconsinClement Zablocki VA Medical Center

Member, NFL Head, Neck and Spine CommitteeNeuropsychology Consultant, Green Bay Packers

MTBI and PCS: Scientific UpdateMichael McCrea, PhD, ABPP-CN1Thank you, Gary, Herb and all of you for having me this morning.

Once again, Im lucky enough to the one telling our story this morning, but the BP and this presentation really reflect the combined work of the entire Neuroscience Center team, along with help from Ken, Gary, Herb, Kasey and Claire, Brad Treichel and several others from Decision Support and Finance.

I have to tell you that I went home last night feeling like things were pretty well in place with the business plan itself and todays presentation, but then I was reminded that theres always room for improvement. I was explaining to our 5 year old, Grace, that I would not likely see her this morning because I planned to get a real early start to a big day when Id be having an important meeting with all the people I work for. I said wish me luck, to which she looked me dead in the eye and replied, you really should have gotten a haircut for this.

Old Problem

New AwarenessBetter Science

In Vivo Study of Acute Brain Injury

Alternative Paradigms for mTBI Research

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Evidence-based Injury Assessment, Management and Return to PlayScience Driving Best Practice!

New Frontiers in the Assessment and Management of Sport-Related Concussion

Corrected summary data file received in May, 2012

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Translational Research Advancing the Science to Benefit all Populations at Risk of mTBI

Where Do We Go From Here?

Future Directions in TBI Research: Acute Effects, Recovery, & OutcomeTRUE NATURAL HISTORY OF INJURYIn Pursuit of the Perfect BiomarkerClinical Recovery: How long does it take for signs & symptoms to recover?

Physiological Recovery: How long does it take for the brain to recover?+

Giza & Hovda, 2010

How Long Does it Take to Recover?Is Symptom Recovery Really Recovery?Rate of Postinjury Recovery in HS and College Athletes (n=790)Total (%)Cumulative Total (%)Rapid (< 1 day)21.121.1Gradual (> 1 day, < 7 days)64.385.4Prolonged (1 week 1 month)11.997.3Persistent (> 1 month)2.7100.0

Effect Sizes: 0.2 Small, 0.5 Medium, 0.8 Large< 0.3 Difficult to detect in individual patients; large overlap b/n patients and control groupEffect Sizes (d)

Biomarkers of Days Past

Meta-Analytic Studies and Reviews:Frencham, 2004; Belanger et al., 2005; Schretlin & Shapiro, 2005; Broglio et al 2008; Iverson, 2011; Rohling et al 2011Adapted from Iverson, 2011

Effect Sizes: 0.2 Small, 0.5 Medium, 0.8 Large< 0.3 Difficult to Detect in Individual Patients; large overlap b/n patients and control group

New Frontiers in Brain Injury ScienceHow Long Does it Take for the Brain to Recover?

LIKE HOW CLEAN THIS IS much better than what I had but what is lost in the grouping of all the images into one box is the message that there are a lot of different diagnostic tools and rehab equipment. Is there a way to pull off something like what I had before, but cleaner?10

A Prospective Study of Advanced MRI Biomarkers to Determine Acute Physiological Effects and Longitudinal Recovery after Sport-Related Concussion

PI: M. McCreaCo-I: A. Nencka, K. Koch, T. Muftuler, Y. Wang, S. Li, T. Hammeke, K. Guskiewicz, T. McAllister

PRE-INJURY:

Normal Cerebral Function

ACUTEIMPAIRED: Elevated symptoms, functional impairment, physiological dysfunction

CONCUSSIVE EVENTCOMPENSATORY:Full clinical recovery, but persistent physiological dysfunctionPOST-ACUTE(Common Time Point for Return to Play)FULLCOMPLETE:Full clinical recovery, normal physiological functionPrevention-based Return to Activity

Integrated mTBI Recovery ModelInjury Management: How Long is Long Enough?

TBI Biomarkers: Same Ole Burning QuestionsSENSITVITY: Will modern biomarkers prove more sensitive than existing clinical measures as the objective marker of injury and measure of recovery?Will neuroimaging prove to be the elusive physiological marker of Postconcussion syndrome?

SPECIFICITY: How unique to mTBI are the abnormalities detected on biomarkers?How are biomarker results influenced by non-injury factors? What is the likelihood of false positives (e.g., depression, anxiety, PTSD, AODA, etc.?)What is the incremental value of biomarkers at the individual case level?

Translational Significance? Clinical Utility at the Individual Case Level

TBI Pathophysiology: Chasing Moving Targets

Axonal Injury

Synaptic Injury Markers(Sypt-1)

Microgliosis-Neuroinflammation Markers(EAMP-II)

Vascular injury Markers(N-CAM)

UCH-L1

SBDP150

SBDP120

GFAP(Banyan)CNPase.

MAP2

Acute markers

Subacutemarkers

BA-0293Chronic markers

DemyelinationNeuronal cell body damageDendritic injuryGliosis / Glial Injury1Demyelination MBP fragment

10% take > 7 days to recoverAcute severity predicts subacute recovery (LOC, PTA, 24 hr GSC)2.5% symptomatic > 45 daysNo impairment on objective measures at Day 45 relative to BLPredicting Risk and Recovery

Real Life Neurobiopsychosocial Model

Nelson et al., 2015, in preparation

NeurobiologicalPsychosocial2,055 athletes baseline tested; 127 concussed athletes re-evaluated with detailed clinical assessment battery < 24 hours and days 8, 15, and 45) after injury.

Risks of Persistent Symptoms After SRCPredictors of Persistent Symptoms >45 Days:

Pre-injury Baseline BSI-18 Somatization Index Score (p=.004)(N=72)McCrea 2014 UnpublishedFaintness or dizzinessPains in heart or chestNausea or upset stomachTrouble getting your breathNumbness or tingling in parts of your bodyFeeling weak in parts of your body

After Controlling for BL BSI-18 (SOM)Acute Injury Characteristics, Assessment Results Not Predictive of Persistent Symptoms

NeurobiologicalPre-Injury Factors

- Genetics- Neurologic Vulnerabilities Trauma Burden

- Injury Severity- Repetitive Exposure- PolytraumaBiomarkers

- Structural/ Functional Imaging- Blood BiomarkersPsychosocialPsychological Function

- Premorbid- Post-injury ComorbiditiesEnvironmental Factors

- Social Support- Life Stressors- IatrogenesisMotivational Factors

- Expectation- Secondary GainMulti-Domain Predictor VariablesNeurobiopsychosocial Model of mTBI:Multidimensional Prediction of Risk & Recovery

Neurocognitive FunctionNeurobehavioral FunctionPsychological Health and WellnessLife Function & QualityNeurologic HealthMulti-Dimensional OutcomeIn A Single Study Design?

CARE Consortium

Sponsored by United States Department of Defense (DoD)& National Collegiate Athletic Association (NCAA)

3 Years, $28M

Advanced Research Core (ARC)Medical College of Wisconsin(McCrea, PI)Virginia TechPIs: Duma & RowsonUNCPIs: Guskiewicz & MihalikUCLAPIs: Giza & DiFioriHead Impact Measurement (HIM)

Co-Leaders: Duma, StemperAdvanced Neuroimaging (MRI)

Co-Leaders: Koch, SaykinBiomarkers & Genetics(BIOGEN)

Co-Leaders: Foroud, GizaARC Scientific ConcentrationsWisconsinPI: BrooksARC Performance SitesARC Coordinating CenterNCAA-DoD Grand Alliance CARE ConsortiumClinical Outcomes(CLIN)

Co-Leaders: Broglio, GuskiewiczSenior Scientific Advisory PanelIverson, Jordan, Kelly, Marshall, Saykin, Smith, Talavage, Wallace, XuCARE Consortium investigators and SSAP members engaged with respective ARC Scientific Concentrations

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ARC Overview: Specific Aim

CARE Aim 3:

Utilize the framework of the CSC (Aim 2) to conduct advanced scientific studies which integrate biomechanical, clinical, neuroimaging, neurobiological and genetic markers of injury to advance our understanding of neurophysiological effects and recovery after SRC in college athletes.

Toward Integration: Neurobiopsychosocial Study of SRC

Understanding the True Natural History of Acute Injury & Recovery

Looking to Science for AnswersConcussion news worries parents

OTL survey finds 57 percent of parents less likely to allow kids to play football

August 26, 2012, 9:13 AM ETBy Paula Lavigne | ESPN.com

Outside the Lines" survey finds that a majority of parents are concerned enough about news reports of concussions from playing football to keep their children away from the sport.

?At a Crossroads

Thank YouMichael McCrea, PhD, ABPPProfessor of NeurosurgeryDirector of Brain Injury ResearchMedical College of Wisconsin

Office: 414-955-7302Email: mmccrea@mcw.edu

Real Life Neurobiopsychosocial Model: NFL CombinePhysical Attributes (height, weight, wings) Vulnerabilities (prior injury/exposure) Biometrics(laboratory results) Performance (speed, strength, agility) Intelligence(aptitude, academics) Personality/EQ (emotional intelligence) Social Maturity(off-field factors) Individual Factors(background/history) Objective: Multi-Dimensional Model to Predict Outcome

Post-injuryPremorbidStructural Brain DamageNeuro-metabolic FactorsDepression/ AnxietyPTSD / StressOrtho / Chronic PainPersonality FactorsMedication EffectsIatrogenic EffectsNocebo Effect / Dx ThreatTBI Symptom Recovery, Functional OutcomeGood Ole Days BiasReinforced Role BehaviorExpectations & MisattributionSymptom ExaggerationMalingering, 2ndary GainFactors Influencing Recovery and Outcome After TBI

Adapted from Iverson, Zasler, Lange, 2008

Somatiz-ationMethods to Assess

Injury-Related FactorsPsychological ComorbiditiesSocialFactorsMotivational Factors

Bringing It All TogetherIn A Single Study Design?

PathophysiologyDiagnosticsInjury ManagementLong-range RisksPH: Education and PreventionInjury BiomechanicsRecovery & Outcome

SPORT CONCUSSION SUMMIT September 24, 2015

#uminjuryctr

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