1. Top Ten Reasons God Did Not Get Tenured 1. He had only one major publication. 2. It had no references. 3. It wasn't published in a refereed journal. 4. Some even doubt he wrote it himself. 5. It may be true that he created the world, but what has he done since then?

2. Top Ten Reasons God Did Not Get Tenured 6. His cooperative efforts have been quite limited. 9. When one experiment went awry he tried to cover it up by drowning the subjects. 8. His office hours were infrequent and usually held on a mountaintop. 7. The scientific community has had a hard time replicating his results. 10. He never applied to the Ethics Board or IRB for permission to use human subjects.

3. Concussion in Sports- Neuropsychiatric Implications: Where we are, where we are going 1 st International Conference on Translational Medicine Nov. 3, 2010 Canberra, Australia David Baron Director, Global Center for Exercise, Psychiatry and Sport USC WPA

4. Goals and Objectives Discuss Translational Process Over view of Concussion in Sports

5. Translational Process Original concept –Bench to bedside Expanded to public health –Culture change Preclinical scientists> clinicians>policy makers(health and governmental)>educators Avoid State of the Shelf science –Blind man and the elephant phenomena

6. Concussion: Introduction An estimated 1.6- 3.8 million sports- related concussions occur annually in the United States 86,000- 134,000 of these concussions are sustained by high school students Acutely, concussions can cause a broad range of psychiatric defects, including depression, anxiety, and cognitive impairment

7. Concussion: Introduction Long term consequences of multiple concussions or multiple subconcussive blows are potentially more serious, with the deposition of tau deposits throughout the brain, and resultant early onset dementia and movement disorders

8. Definition of Concussion (International Consensus) A complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces Caused by direct blow to the head, face, neck, or elsewhere on the body with “impulsive” force transmitted to the head.

9. Definition of Concussion (International Consensus) Often rapid onset Often short-term impairment of neurologic function that resolves spontaneously May result in neuropathological changes, but acute clinical symptoms reflect functional disturbance rather than structural

10. Definition of Concussion (International Consensus) Results in graded set of clinical symptoms May or may not involve loss of consciousness Resolution of clinical and cognitive symptoms typically follows sequential course

11. Definition of Concussion (International Consensus) Small percentage of cases have prolonged post-concussive symptoms (10-20%) No abnormality found on standard structural neuroimaging (CT or standard MRI)

12. Classification of Concussion At least 25 grading systems currently in use Aimed at characterizing concussion severity and prognosis –And subsequently return to play decisions No scientific agreement on which is best

13. International Conferences on Concussion in Sport- Issues addressed Definition Classification Evaluation Management Modifying Factors –Factors that may alter evaluation and management –Factors that predict prolonged or persistent symptoms

14. Is There any Consensus on Concussion? 3 separate conferences in last 9 years aimed at reaching consensus of understanding and management of sports concussions Consensus decisions reached by votes from a panel of international concussion experts (Concussion in Sports Group or CISG)

15. Is There any Consensus on Concussion? –1 st International Conference on Concussion in Sport, Vienna 2001 –2 nd International Conference on Concussion in Sport, Prague 2004 –3 rd International Conference on Concussion in Sport held in Zurich, November 2008

16. Classification of Concussion The international Concussion in Sports Group (CISG) does not endorse any single grading system Concussion severity can only be determined in retrospect: –After all concussion symptoms clear –After neurological examination normal –After cognitive function returns to baseline

17. Concussion Laws

18. In October 2007, under pressure from congress and media NFL made dramatic changes in its handling of concussion –For the first time acknowledged that concussions lead to long-term problems –Return to play decisions made only by a independent neurologists –Resignation of NFL Concussion Committee’s 2 co-chairmen

19. Concussion Laws In May 2009, the state of Washington passed a new bill called the Lystedt Law –Requires any youth showing signs of a concussion be examined and cleared by a licensed health care provider before being allowed to return to play

20. Concussion Laws –Named after Zackery Lystedt, a young athlete permanently disabled after sustaining a concussion in 2006, and prematurely returning to the game

21. Chronic Traumatic Encephalopathy

23. ALS or CTE? Doctors at Veterans Affairs Medical Center in Bedford, MA and Boston University School of Medicine recently discovered by autopsy that 2 NFL players and 1 boxer diagnosed with ALS really had a variant of CTE Similar findings in deceased soldiers previously diagnosed with ALS

24. Chronic Traumatic Encephalopathy (CTE) First described by Dr. Harrison Stanford Martland, a pathologist, in 1928 (“punch drunk syndrome”) Later called “Dementia Pugilistica”, and more recently, “Chronic Traumatic Encephalopathy” An estimated 17% of retired professional boxers will develop chronic traumatic encephalopathy

25. Chronic Traumatic Encephalopathy Highest incidence in boxers and NFL linemen, although cases have been described in a soccer player, wrestler, epileptics, head bangers, and domestic abuse victims

26. Chronic Traumatic Encephalopathy May result from single concussion, although more frequently results from repeated concussions or subconcussive blows Can present upon retirement or years later

27. Chronic Traumatic Encephalopathy Common presenting symptoms include: –memory loss –irritability –outbursts of aggressive or violent behavior –confusion –speech abnormalities –cognitive decline/dementia –gait abnormalities

28. Chronic Traumatic Encephalopathy Often times there is a mood disturbance as well: –depression (often with suicidal ideation) –bipolarity Often accompanied by psychosis in the form of paranoid ideation Often times culminates in suicidal behavior

29. Chronic Traumatic Encephalopathy Microscopic Pathology: neuronal loss and gliosis with Tau deposition Hippocampus, entorhinal cortex→ memory disturbances Amygdala→ mood disorders Frontal and Temporal cortices→ dysexecutive symptoms, cognitive deficits Substantia nigra→ parkinsonism Brainstem white matter tracts (including cerebellar tracts)→ Ataxia, gait abnormalities

30. Chronic Traumatic Encephalopathy Gross brain pathology (may or may not have) –Reduction in brain weight –Enlargement of lateral and 3 rd ventricles –Thinning of Corpus callosum –Cavum septum pellucidum with fenestrations –Scarring and neuronal loss of cerebellar tonsils

31. Tau Deposits: Frontal Lobe ↙ ↙ ↙ ↙ ↙ ↙ ↙ ↙ ↙

32. Tau Deposits: Brain Stem ↙↙ ↙ ↙ ↙ ↙

33. Pathophysiology No existing animal or experimental models (not fully elucidated) Impaired neurotransmission –Excessive release of excitatory neurotransmitter glutamate Neurotoxicity Opening of ion channels, leading to dysregulation of ions in the brain

34. Pathophysiology Dysregulation of ions –Causes strain on ion pumps Leads to increased energy demand Hypermetabolic state –Larger than normal amounts of glucose consumed Reduction of cerebral blood flow –Combined with hypermetabolic state, results in “energy crisis”

35. Translational issues Need better longitudinal data on consequences of multiple sub-clinical concussions Need to change culture in collision sports-acknowledge the long term risks Data needed from pitch to bench