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?

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.

Concussion in Sports-Neuropsychiatric Implications: Where we are, where we are going

1st International Conference on Translational MedicineNov. 3, 2010 Canberra, Australia

David BaronDirector, Global Center for Exercise, Psychiatry and SportUSCWPA

Goals and Objectives

Discuss Translational Process

Over view of Concussion in Sports

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

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

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

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.

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

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

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)

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

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

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)

Is There any Consensus on Concussion?

– 1st International Conference on Concussion in Sport, Vienna 2001

– 2nd International Conference on Concussion in Sport, Prague 2004

– 3rd International Conference on Concussion in Sport held in Zurich, November 2008

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

Concussion Laws

Concussion Laws

• 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

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

Concussion Laws

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

Chronic Traumatic Encephalopathy

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

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

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

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

Chronic Traumatic Encephalopathy

• Common presenting symptoms include:– memory loss– irritability– outbursts of aggressive or violent behavior– confusion– speech abnormalities– cognitive decline/dementia– gait abnormalities

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

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

Chronic Traumatic Encephalopathy• Gross brain pathology (may or may

not have)– Reduction in brain weight– Enlargement of lateral and 3rd ventricles– Thinning of Corpus callosum– Cavum septum pellucidum with

fenestrations– Scarring and neuronal loss of cerebellar

tonsils

Tau Deposits: Frontal Lobe

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Tau Deposits: Brain Stem

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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

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”

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