Stephen E. Olvey, M.D. Associate Professor of Clinical Neurology/Neurosurgery

1. THE IMPORTANCE OF MILD TBIRECOGNITION AND MANAGEMENT OF SPORTS RELATED CONCUSSION AND THE MYSTERY OF CTE Stephen E. Olvey, M.D. Associate Professor of Clinical Neurology/Neurosurgery Founding Fellow FIA Institute for Motor Sport Safety and Sustainability, Paris Scientific Advisory Panel, NOCSAE Chief Medical Officer U.S. Grand Prix, Austin

2. CONCUSSION or MILD TBI

3. WHY THIS IS A HOT TOPIC? • There are > 1 million sports related mTBIs reported annually in the U.S alone. Millions more worldwide. • Sports concussion is unique in that it appears to be mild, but carries a high risk of recurrent concussion and possible subsequent chronic illness due to early return to competition and too many concussions, too close together. • Long term dysfunction may follow repeated clinical and sub-clinical concussions. Estimated that up to 20% of retired NFL players have early dementia. • >98% of sports related head injuries are concussions. • Misunderstanding of concussion still permeates the medical profession.

4. FOOTBALL AS A MAJOR ISSUE An estimated 4.5 million children play football in organized games each year in the U.S. In 2007, 920,000 athletes under age 18 were treated in ER,s and physician offices for football related injuries. Girl’s soccer, ice hockey are 2nd and 3rd. 47% had suffered at least one concussion and 35% had more than one. Actual numbers are likely much higher. One Canadian hockey study revealed 21.5/1000 exposures. – Echlin, Neurosurgery Focus, 2012 Post suicide18 yo found at autopsy to have changes compatible with chronic traumatic encephalopathy.

5. FOOTBALL CONTINUED • NEURODEGENERATIVE MORTALITY RATE IN PROFESSIONAL FOOTBALL PLAYERS IS 3 X THAT OF THE GENERAL POPULATION! • INCIDENCE OF ALZHEIMER’S AND ALS IS 4X THAT OF THE GENERAL POPULATION! -Lehman et. al. Neurology, 2012

6. CLINICAL DILEMMA • Growing health problem in all contact sports. • No proven acute treatment. Injury must run its course. • Severity of a concussion is not known until it has resolved. The final outcome may take years. • Uncertainty remains about when it is safe to return to competition. • Multiple criteria and guidelines exist; all based primarily on subjective, clinical factors and the duration of impairment. They do not, unfortunately correlate with outcome. • No one knows what officially constitutes a “concussion”.

7. OLD DEFINITION “A reversible injury to the brain due to traumatic forces resulting in amnesia and/or loss of consciousness.”

8. NEW DEFINITION “ A clinical syndrome of biomechanically induced alteration of brain function, typically affecting memory and disorientation, which may involve loss of consciousness.” - American Academy of Neurology, 2013

9. EXPANDED DEFINITION • Don’t need to have been unconscious. • Don’t need to have directly hit your head. • Don’t need to have been amnesic. • Must have some concussion related symptoms. • Normal routine CT or MRI is the rule. • May or may not have post concussion symptoms. • Repeated sub-clinical head accelerations will likely become part of the definition in the near future. -4th International Conference on Concussion

10. CHRONIC TRAUMATIC ENCEPHALOPATHY • Known since 1928 as Dementia • Pugilistica. (Boxers almost exclusiviely) • Growing issue in contact sports as well as • military exposure to IED’s. • Major health, legal, financial, and moral issue. • Currently can only be diagnosed on post • mortem examination. • Majority opinion is that CTE can be • prevented with timely recognition and treatment • of concussions, and improved methods of • prevention.

11. CTE • Currently, no large scale epidemiological studies have been done. • Problem is: Until recently, concussion was thought to be rather innocuous. • Multiple studies are now in progress. • Comprehensive review in Journal of Neuropathology, Exp. Neurology, 2010 citing, 118 references

12. CTE Work utilizing survey research from the Center for the Study of Retired Athletes has shown that both mild cognitive impairment and depression are more common than expected in age-matched controls and that a higher incidence is associated with 3 or more concussions. -Bailes, et. al. J Neurosurg. 11/13

13. CTE CURRENTLY DEFINED • A degenerative brain disease associated with repeated brain trauma both clinical and sub-clinical in nature often beginning in early childhood. • Stepwise deterioration in memory, insight, judgment, development of movement disorders, and finally full blown dementia. • Presence of an abnormal protein called “tau” in the form of neurofibrillary and astrocytic tangles often perivascular in location. Decreased brain weight • Eventually leads to progressive cellular death.

14. Middle aged, NFL player post suicide 73 yo champion boxer No CTE

15. BOSTON UNIVERSITY STUDY • 68 CASES OF CTE STUDIED EXTENSIVELY • AGES: 17 – 98 • 50 FOOTBALL PLAYERS 33 IN NFL, 9 COLLEGE, 6 HS, 4 NHL, 8 BOXERS, 6 VETERANS OF IRAQ, AFGANISTAN • ASSOCIATION FOUND WITH ALZHEIMERS AND ALS. 4X THAT OF THE GENERAL POPULATION. Ann McKee, Director CSTE (Center for the study of traumatic encephalopathy)

16. FAMILY INTERVIEWS • STAGE 1: Persistent headaches and inability to concentrate. • STAGE 2: Depression, explosive behavior, and short term memory impairment. • STAGE 3: Executive function, judgment, multitasking, worsening cognitive issues. • STAGE 4: End stage dementia (89% of subjects followed this pattern)

17. NOT JUST A BUMP ON THE HEAD • Potassium, glutamate, and glucose are immediately released from affected brain cells… • Calcium enters these disturbed cells in exchange for the K+… • Neurotransmitter release occurs with loss of auto-regulation in the area of the brain affected. • Concomitant decrease in regional cerebral blood flow with a resultant energy crisis…

18. INJURY AFTERMATH • Brain is vulnerable to further injury during this period due primarily to altered cerebral glucose metabolism. (20 minutes to several days?) • The hyperglycolysis that results, depletes cellular ATP resulting in an energy crisis. Decreased blood flow in the area limits the brain’s ability to supply enough glucose to satisfy the normal supply/demand relationship. Rise in lactate. • The result is seriously altered brain function. • If “too much” calcium influx, neuronal cell death may occur; seen in the most severe forms of concussion

19. POSSIBLE ROLE OF INFLAMASOMES • Recently discovered intracellular protein bundles thought to be the precursor's to the inflammatory cascade – the “IL Gang”. • Unknown what triggers what inflamasome. • Thought to cause long term derangements in the brain due to an inflammatory reaction that occurs in stages and develops more extensively with repeated insults too close together. (Immunocytotoxicity, “primed glial cells”) - Blaylock, Maroon, Surg, Neurology, Int. 2011

20. PATHOPHYSIOLOGY SUMMARIZED • There is a period of energy crisis and vulnerability during which secondary insults must be avoided (persistent “primed” glial cells) - return to play issues • Post- mild traumatic physiological brain abnormalities in humans can last days to months. • Clinical assessment is inadequate to quantify post traumatic dysfunction. • Excessive activation or forced disuse of injured brain can worsen the outcome - therapeutic implications • The developing brain is uniquely vulnerable to trauma.--- It is different in kids!

22. THERAPUTIC IMPLICATIONS

23. WHAT HAPPENS IF CONCUSSED ANIMAL IS CONFINED POST INJURY? WHAT HAPPENS IF AN ANIMAL IS CONFINED POST INJURY?

25. BIOMECHANICS • Translational (linear) • Rotational (rare) • Angular (combined)

26. TWO TYPES OF ACCELERATION APPLICATION • Impulsive loading, now called non-contact loading (whiplash, shaking baby), and Impact loading (skull vs. a hard surface) • In general impact loading produces much higher forces than does impulsive loading. Significant TBI can result from both!

27. NON-CONTACT (IMPULSIVE) LOADING No direct impact to the head, head placed in motion by impact directed elsewhere, no skull deformation

28. Shaken Baby Syndrome

29. PREVENTION WHAT GOOD IS A HELMET ANYWAY?

30. HELMETS • HELMET PROTECTS WEARER FROM EXTERNAL IMPACTS. • HELMET LINER ABSORBS SOME OF AN INTERNAL IMPACT (BRAIN IMPACTING SKULL) • HELMET KEEPS YOUR HEAD WARMER • IT IS GENERALLY QUIETER INSIDE THE HELMET. • HELMET ITSELF CAN INFLICT INJURY! • THERE IS NO CONCUSSION PROOF HELMET!!

31. CURRENT TESTS ARE ONLY SOMEWHAT REFINED FROM THIS EARLY TEST METHOD

32. FOOTBALL HELMETS TODAY • BASED ON TESTS DESIGNED IN MID 60’S • MUST PROTECT FROM A FORCE THAT WOULD CAUSE A LINEAR SKULL FRACTURE IN A CADAVER HEAD. • ANGULAR ACCELERATION NOT CONSIDERED. • MINIMAL REFINEMENTS SINCE THE 70’S • WEIGHT GIVEN LITTLE CONSIDERATION. • COME IN SIZES SMALL, MEDIUM, LARGE

33. Wt = >5.5 lbs. Cost = 450.00 Comfort/fit pads Inner liner Shell

34. MOTOR SPORTS HELMETS TODAY • WEIGHT GIVEN GREAT CONSIDERATION . • MULTIPLE LAYERS AND SPECIAL WEAVES TO CREATE GREATER IMPACT PROTECTION. • VISOR PROTECTION (F-18 WINDSHIELD) • CUSTOM FITTED TO INDIVIDUAL DRIVER

35. Wt = 2.2 lbs. Cost = 4500.00

36. CONSIDERATIONS • AT LEAST 30 - 40% OF CONCUSSIONS DO NOT INVOLVE IMPACT AT ALL. NEAR 50% IN RACING • ANGULAR ACCELERATION INCREASES GEOMETRICALLY AS WEIGHT OF A HELMET INCREASES. • FOOTBALL HELMET MUST TOLERATE REPEATED HITS. • RACING HELMET DESIGNED TO WITHSTAND THE “BIG ONE” • LINERS THEREFORE HAVE DIFFERENT REQUIRMENTS. • BRAIN DOES IMPACT INSIDE OF SKULL – SOME AREAS NOT SO FRIENDLY. • SIGNIFICANT SHEARING INJURY OCCURS WITH ANGULAR ACCELERATION FROM BOTH IMPACT AND NON-IMPACT TRAUMA.

37. NEUROPSYCHIATRIC TESTINGFOR DIAGNOSIS • ImPACT: Immediate Post-Concussion Assessment and Cognitive Testing • Now used in NFL, Indy Car, Formula 1, NASCAR, NHL, World Cup Soccer, USSA, FISA, and FIFA. • Most extensively tested (Initially over 18,000 subjects) • Available worldwide in 17 languages 24/7

38. KING – DEVICK TEST • Task of reading numbers in sequence. • Printed on 3 levels of cards. • Can be administered by anyone with simple training. • Quick and dirty assessment.

39. King-Devick vs. ImPACT < 2 minutes 25-35 minutes some learning no learning (neither includes vestibular function/balance important for return to competition)

40. THERE IS STILL NO AGREEMENT ON THE ROLE OF COMPUTER OR PENCIL DERIVED NEURO-PSYCHE TESTING. HOWEVER; DUE TO THE LACK OF ANYTHING ELSE NEARLY EVERY MAJOR SPORTING ATHORITY USES IMPACT BASELINE TESTING AND SUBSEQUENTLY FOR RETURN TO PLAY DETERMINATIONS. VESTIBULAR FUNCTION ALSO REQUIRES TESTING AND NORMALIZATION.

41. PHYSICAL SIGNS OF MILD TBI • Any loss of consciousness • Retrograde or anterograde amnesia • Seizure at time of impact (so-called impact seizure) • Vacant stare • Inability to focus, easily distracted • Slurred speech, slow to answer questions • Disoriented, unsteady gait • Memory deficits, sudden personality change • Emotionally instability, inappropriate behavior • Delayed verbal and motor responses

42. SYMPTAMATOLOGY • Headache ( nearly always present > 90%) • Dizziness, vertigo • Lack of awareness • Nausea, vomiting • Loss of balance BESS; Balance Error Scoring System • Feeling dazed, “dinghy” • Ringing in the ears (tinnitus) • Blurred or double vision (diplopia) • Hyperacusis and/or photophobia • “Just not feeling right”

43. BOTTOM LINE • Examiner must have high index of suspicion based on mechanism of injury, helmet damage if any, damage to surrounding area, inside of vehicle, and behavior of the athlete. • Athletes themselves will under report symptoms and out right lie to stay in the event. • We must train coaches, trainers, other players, and families to recognize TBI

44. MANAGEMENT • ANY Symptoms or Signs: NO RETURN TOANY SPORTS ACTIVITY; whether competition, or training – WHEN IN DOUBT, SIT THEM OUT! • Athlete should be medically evaluated and monitored every 5 min. for symptom/sign resolution or deterioration for at least 1 hr. then with another person to be aware of patient x 24 hours.

45. EFFECT OF REPEATED MILD TBI ON THE ATHLETE • An athlete with more than three previous concussions is 9 x more likely to have associated amnesia either anterograde or retrograde as well as post concussion symptoms – 3 – 9x greater risk for long term disability • Retrograde amnesia: 10 x more likely to have a poor outcome – chronic, long term symptoms • Anterograde amnesia: 4.2 x more likely to have a poor outcome – chronic symptoms • L.O.C. not predictive of outcome!!!

46. WHEN DO WE NEED CT/MRI? • Suspicion of a structural lesion: focal neurological signs, evidence of significant impact i.e. helmet, cockpit damage in racing • Seizure activity > 1 minute • Prolonged disturbance of consciousness or worsening level of consciousness while under observation. • Persistent clinical or cognitive symptoms. Don’t improve gradually over period of 2 to 3 weeks.

47. RETURN TO COMPETITION • Level 1. No activity, complete rest until asymptomatic; once asymptomatic proceed to level 2 • Level 2. Light aerobic exercise such as walking or stationary cycling with helmet on. • Level 3: Sport-specific training, skating in hockey, running in soccer, simulator, go-kart, family car in racing. • Level 4: Return to sport with supervised private practice with attention to consistent, competitive times or abilities. • Level 5: Return to competition under observation during practice first, then competition. • Any re-occurrence of symptoms along the line, athlete must go back to the previous level!!!!

48. WHAT HAVE WE LEARNED • Mild TBI can have long term catastrophic effects. • Most, but not all athletes recover quickly. • Age may be important in recovery. Old is bad. • Neuropsychological testing is a useful tool. • Management should involve multiple components. • Total inactivity is bad but, activity too soon is also bad.

49. WHAT WE STILL DON’T KNOW • How many mild TBI’s are too many? • How close together is too close? • When is the brain really back to normal? • Is there effective pharmacotherapy? (Anti-inflamatories, neuro-protective agents) • Why some athletes are “brain injury prone”? - The exact role of age/development (kids and women are more vulnerable) - The role of genetics, seems to run in families - The role of other conditions (migraine, ADD, APOE- e4; all appear to be risk factors)

50. PREVENTION Stay inside and don’t do anything or Wear an approved/well fitted helmet in contact sports. Head and Neck restraint SYSTEM in 4 wheel vehicles. Newer devices now available for motorcycles. Recognize concussion and get out of the game. No return to activity until asymptomatic and NP test is back to baseline. Rule changes in football, hockey.