How to Distinguish Post- Concussion Syndrome from CTE/ When to Retire

H Robert C. Cantu, MA, MD, FACS, FACSM, FAANS Clinical Professor of Neurosurgery and Neurology Co-Founder, Medical Director Co-Founder-Clinical Diagnostics and Therapeutics Concussion Legacy Foundation Leader CTE-AD Center Boston University School of Medicine Member Independent Concussion Advisory Group World Rugby Medical Director and Director of Clinical Research Dr. Robert C. Cantu Concussion Center Senior Advisor, NFL Head Neck & Spine Committee AssocCTE. Chairman, Dept. of Surgery, Chief, Neurosurgery Service Member, NFLPA Mackey-White TBI Committee Director of Sports Medicine Emerson Hospital, Concord, MA Senior Advisor Brain Injury Center Children’s Hospital, Boston MA Medical Director National Center for Catastrophic Sports Injury Research VP and Chair Scientific Advisory Committee Adjunct Professor National Operating Committee on Standards for Dept. of Exercise and Sports Science, UNC Chapel Hill Athletic Equipment ( NOCSAE )

S Disclosures

Senior Advisor NFL Head Neck & Spine Committee VP NOCSAE and Chair Scientific Advisory Committee Co-Founder, Medical Director Concussion Legacy Foundation Royalties Houghton Mifflin Harcourt Legal Expert Opinion (NCAA, NHL etc.) National Collegiate Athletic Association Studen-Athlete Concussion Injury Litigation (Medical Science Committee) What is it? What is the cause? When do symptoms appear? How long do symptoms last? Concussion

A type of traumatic brain Caused by a bump, blow, or jolt to Leads to short- or long-term symptoms Most people feel better within a couple of injury. the head, or by a hit to the body that appear immediately, or soonvs. after weeks, and symptoms generally get better CONCUSSION that causes the head and brain to the injury. over time. move rapidly back and forth. PCS Post Concusssion “ “ Concussion S/S lasting overvs 1 month Usuall months, sometimes years, rarely permanent Syndrome CTE

CTE A neuro- Linked to repetitive head or brain Symptoms show up years, or decades, Symptoms may vary based on the age of the Degener-ative brain injuries, including concussions. after the repetitive head impacts were person and often get worse over time. disease. experienced. Take away message 3:

Concussion is both a pathophysiologic metabolic as well as a structural injury

Neurometabolic Cascade of Concussion Giza and Hovda (2001) Impact

Growth

Time Impact

Growth

Time Number of Publications in Pubmed with “Chronic Traumatic Encephalopathy” or “Dementia Pugilistica” as Keywords Total = 643 (88% NOT BU) Where are we now?

• Fears • Misconconceptions • Hype • Too Much Concern? • OR • Too Little Concern? • Too Much Focus on Concussion? • Too Little Focus on Subconcussive Trauma • Misconceptions about what CTE is (by both lay and medical communities) CTE: What do we think we know? Chronic Traumatic Encephalopathy is Dementia Pugilistica

• Neurodegenerative disease, similar to Alzheimer’s disease, but it is a unique disease • CTE is associated with a history of repetitive head impacts, including concussions and subconcussive trauma • The repetitive trauma appears to start a cascade of events in the brain that eventually leads to progressive destruction of brain tissue Is CTE is a distinct tauopathy that can be distinguished from other tauopathies Pathological Criteria for the Diagnosisof CTE the Pathologicalfor Criteria NINDS/NIBIBConsensus McKee et al. Acta Neuropathologica 2016 Neuropathologica Acta et al. McKee Meeting Evaluate to

? February 25-6, 2015 Pathognomonic Lesion of CTE

“In CTE, the tau lesion considered pathognomonic was an abnormal perivascular accumulation of tau in neurons, astrocytes, and cell processes at the depths of the depths of the cortical sulci in an irregular pattern.” Is CTE is a distinct tauopathy that can be distinguished from other tauopathies Pathological Criteria for the Diagnosisof CTE the Pathologicalfor Criteria NINDS/NIBIBConsensus McKee et al. Acta Neuropathologica 2016 Neuropathologica Acta et al. McKee Meeting Evaluate to

? February 25-6, 2015 Pathognomonic Lesion of CTE

“In CTE, the tau lesion considered pathognomonic was an abnormal perivascular accumulation of tau in neurons, astrocytes, and cell processes at the depths of the depths of the cortical sulci in an irregular pattern.”

Referrals

Physical Therapy

Graded Exercise Cervicogenic Return to Play Vestibular Protocol • Physical Therapy – Vestibular Rehabilitation – Cervicogenic Headache Assessment – Strengthening of neck/spine – Return to Activity Protocol • Occupational Therapy – Treatment of visual and oculomotor dysfunction. • Cognitive Therapy – Evaluation and treatment of cognitive dysfunction. – Formulation of school and work plans. Pharmacologic Treatment of Concussion, PCS, Later Life Effects of Repetitive Head Trauma Cognition Emotionality Methylphenidates: Ritalin 10-20ER, Addarol 5-20mg/d, Strattera (Atomoxetine) 40-80 mg/d, Concerta 18mg/d, Vyvance 20-30 Explosiveness/Agitation/Anxiety mg/d, Lexapro 10-20mg/d (not under 12) Amantadine 100mg bid. Donpezil (Aricept) 5mg – 10mg/d Zoloft (sertraline) 25-50 mg/d Memantine (Namendia) 5mg-10mg bid If SSRI’s not working risperidone .5-6mg/d Sleep Depakote 500-1000mg/d ER Melatonin 3-6mg hs Pseudobulbar Trazadone 50-150mg hs Nuedexta (20mg dextromethorphan) 10 mg quinine 1cap/d 7d, Ambien 5-10 mg hs then bidresperidone 0.5-6mg/hs then bid Nuedexta (20mg dextromethorphan) 10 mg quinine 1cap/d 7d, Somatic Depression Amitriptyline 10-25mg hs Lexapro (escitalopram) 10-20mg/d (not under 12) Neurontin 100 or 300mg up to 1000 /d Zoloft (sertraline) 25-50 mg/d Lexapro (escitalopram) 10-20mg/d (not under 12) Cymbalta (duloxetine) 20mg bid Zoloft (sertraline) 25-50 mg/d Inderal 10-60 mg/d Prozac (fluoxetine) 20-80 mg/d Propranolol 80-160mg/d Verapamil 80-160 mg/d JAMA Neurology 2019 Association of White Matter Rarefaction, Arteriolosclerosis, and Tau With Dementia in Chronic Traumatic Encephalopathy Michael L. Alosco, PhD; Thor D. Stein, MD, PhD; Yorghos Tripodis, PhD; Alicia S. Chua, MS; NeilW. Kowall, MD; Bertrand Russell Huber,MD, PhD; Lee E. Goldstein, MD, PhD; Robert C. Cantu, MD; Douglas I. Katz, MD; Joseph N. Palmisano, MPH, MA; Brett Martin, MS; Jonathan D. Cherry, PhD; Ian Mahar, PhD; Ronald J. Killiany, PhD; Michael D. McClean, ScD; Rhoda Au, PhD; Victor Alvarez, MD; Robert A. Stern, PhD; Jesse Mez, MD, MS; Ann C. McKee,MD

Importance Pathways to dementia in CTE are unclear and likely involve tau and non tau pathologic conditions.

OBJECTIVE To investigate the association of white matter rarefaction and cerebrovascular disease with dementia in deceased men older than 40 years who played football and had CTE.

DESIGN, SETTING, AND PARTICIPANTS This is a cross-sectional study of 224 men who played football and were neuropathologically diagnosed with CTE.

EXPOSURES The number of years of football play as a proxy for repetitive head impacts.

MAIN OUTCOMES AND MEASURES Neuropathological assessment of white matter rarefactionand arteriolosclerosis severity (on a scale of 0-3, where 3 is severe); number of infarcts,microinfarcts, and microbleeds; and phosphorylated tau accumulation determined by CTE stage and semiquantitative rating of dorsolateral frontal cortex (DLFC) neurofibrillary tangles(NFTs) (none or mild vs moderate or severe). Informant- based retrospective clinica lnterviews determined dementia diagnoses via diagnostic consensus conferences. JAMA Neurology 2019

Association of White Matter Rarefaction, Arteriolosclerosis, and Tau With Dementia in Chronic Traumatic Encephalopathy Michael L. Alosco, PhD; Thor D. Stein, MD, PhD; Yorghos Tripodis, PhD; Alicia S. Chua, MS; NeilW. Kowall, MD; Bertrand Russell Huber,MD, PhD; Lee E. Goldstein, MD, PhD; Robert C. Cantu, MD; Douglas I. Katz, MD; Joseph N. Palmisano, MPH, MA; Brett Martin, MS; Jonathan D. Cherry, PhD; Ian Mahar, PhD; Ronald J. Killiany, PhD; Michael D. McClean, ScD; Rhoda Au, PhD; Victor Alvarez, MD; Robert A. Stern, PhD; Jesse Mez, MD, MS; Ann C. McKee,MD

RESULTS Moderate to severe white matter rarefaction (84 of 180 [46.6%]) and arteriolosclerosis (85 of 180 [47.2%]) were common; infarcts, microinfarcts, and microbleeds were not. A simultaneous equations regression model controlling for age and race showed that more years of play was associated with more severe white matter rarefaction (β, 0.16 [95%CI, 0.02-0.29]; P = .03) and greater phosphorylated tau accumulation (DLFC NFTs: β, 0.15

[95%CI, 0.004-0.30]; P = .04; CTE stage: β, 0.27 [95%CI, 0.14-0.41]; P < .001). White matter rarefaction (β, 0.16 [95%CI,0.02-0.29]; P = .03) and DLFC NFTs (β, 0.16 [95%CI, 0.03-0.28]; P = .01)were associated with dementia. Arteriolosclerosis and years of play were not associated, but arteriolosclerosis was independently associated with dementia (β, 0.21 [95%CI, 0.07-0.35]; P = .003).

CONCLUSIONS AND RELEVANCE Among older men who had played football and had CTE,more years of football play were associated with more severe white matter rarefaction and greater DLFC NFT burden. White matter rarefaction, arteriolosclerosis, and DLFC NFTs were independently associated with dementia. Dementia in CTE is likely a result of neuropathologic changes, including white matter rarefaction and phosphorylated tau,

National Athletic Trainers’ Association Position Statement: Sport-Related Concussion

Kevin M Guskiewicz; Scott L.Bruce; Robert C. Cantu; Michael S. Ferrara; James P. Kelly; Michael McCrea; Margot Putukian; Tamara C. Valovich McLeod

Kevin M Guskiewicz, PhD, ATC, Scott L Bruce, MS, ATC, Robert C. Cantu, MD, Michael S. Ferrara, PhD, ATC, James P Kelly, MD, Michael McCrea, PhD, Margot Putukian, MD, and Tamara C Valovich McLeod, PhD, ATC, contributed to conception and design; acquisition and analysis and interpretation of the data; and drafting, critical revision, and final approval of the article.

Address correspondence to National Athletic Trainers’ Association, Communications Department, 2952 Stemmons Freeway, Dallas, TX 75247

[email protected]) National Athletic Trainers’ Association Position Statement: Sport-Related Concussion

• Section IV: When to Refer an Athlete to a Physician after concussion

• Section V: When to disqualify an Athlete – Disqualifying for the game or practice – Disqualifying for the season – Disqualifying for the career

CANTU, ROBERT Concussion severity should not be determined until all post concussion symptoms have abated. The Lancet Neurology. vol 3, June 2004 So what’s the big problem??

How to determine if the player is truly asymptomatic

CONCLUSIONS

DO NOT return the athlete to competition until:

• Normal neurological assessment • Asymptomatic of post concussion signs/symptoms at rest and exertion • If done, neuropsych battery baseline or above • If done, CT or MIR shows no lesion placing the athlete at increased risk of head injury (edema, hemorrhage, hydrocephalus, cavum spetum pellicidum, arachnoid cyst) CONCLUSIONS

• The most important guideline to remember is that no athlete should return to participation while still symptomatic first at rest and then exertion. This includes the presence of headache related to a concussive episode.

• Any athlete who has experienced LOC or anterograde or retrograde amnesia should not be permitted to return to play that day. CONCLUSIONS

• When making a RTP decision, you must find a balance between what is safe, yet practical. Consider all pieces of the concussion puzzle, and when in doubt, err on the side of caution. “If in doubt, sit them out.” Conclusion The final decision regarding when and if a concussed athlete can return to competition is made on an individual basis and will depend on:

•The athlete’s concussion history •The severity of the injury •The duration of signs and symptoms •The time between injuries •The severity of blow causing concussion •The availability of experienced personnel to conduct repeated assessments and monitoring recovery. CONCLUSIONS

Certified athletic trainers, team physicians, neurosurgeon and neuropsychologists ideally should work together as a team to determine the athlete’s readiness to return safely to competition following a concussion. MEDICAL FACTORS EXTRANEOUS FACTORS Symptoms (Observed & Reported) Radiological findings Field conditions / type Physical findings + Playing surface +

Neuropsychological Data +

CONCUSSION FACTORS RETURN TO PLAY Severity of injury (PTA, RTP, LOC) Time from concussion History of concussions (number, + + spacing, severity)

PLAYER FACTORS Career aspirations TEAM FACTORS Personality Level of play (Elite v. recreational) Style of play Position of player on team Physical symptoms Importance of game Family issues Opposing team characteristics Feelings re: return to play Sport specific risk for concussion Relative Contraindication to Return to Play after Concussion

Duration of post concussion symptoms progressively last longer (months not days)

Mild indirect blows (not directly to head) produce post concussion symptoms. Absolute Contraindication to Return to Play after Concussion DO NOT return athlete to collision practice or competition until: • Normal neurological assessment •Asymptomatic of post concussion signs/symptoms at rest and exertion •If done neuropsyche battery baseline or above •If done CT or MRI shows no lesion placing athlete at increased risk of head injury (edema, hemorrhage, hydrocephalus, cavum septum pellicidum, arachnoid cyst) Thank You!