Chronic Traumatic Encephalopathy (CTE): Clinical, Pathophysiologic and Therapeutic Aspects

1. Chronic Traumatic Encephalopathy (CTE): Clinical, Pathophysiologic and Therapeutic Aspects Patricio F. Reyes, MD, FAAN Program Director HealthPartners Medical Group St. Paul, MN

2. Affiliations Yuma Pharmaceuticals Chief Medical Officer Chair, Scientific Advisory Board Retired Players Association (NFL) Chief Medical Officer Board Member Association of Ringside Physicians Board Member

4. Last updated 2 days ago From Wikipedia, the free encyclopedia Jump to: navigation, search Tiaina Baul "Junior" Seau Jr. (; January 19, 1969 – May 2, 2012) was a linebacker in the National Football League (NFL) who became a San Diego sports icon. Known for his passionate playing style,12 he was a 10-time All-Pro, 12-time Pro Bowl selection, and named to the NFL 1990s All-Decade Team. Of Samoan descent, Seau played college football at the University of Southern California. He was taken by the San Diego Chargers as the fifth overall pick of the 1990 NFL Draft. Seau starred for 13 seasons for the Chargers before being traded to the Miami Dolphins, where he spent three years before four final ones with the New England Patriots. Seau retired from pro football in 2010. A standout

5. What is Dementia Pugilistica (DP)? • “boxer’s syndrome,” • “punch-drunk syndrome,” • “chronic boxer encephalopathy,” • “traumatic boxers encephalopathy.” • Can mimic Alzheimer’s disease • Can mimic Parkinson’s disease • Chronic Traumatic Encephalopathy

6. Need to cite this story in your essay, paper, or report? Use one of the following formats: APAMLA given Boston University (2009, January 27). Football And Progressive Brain Damage: Tom McHale Of NFL Suffered From Chronic Traumatic Encephalopathy When He Died In 2008. ScienceDaily. Retrieved June 21, 2012, from http://www.sciencedaily.com­/releases/2009/01/090127165938.htm Note: If no author is, the source is cited instead. Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff. enlarge How dangerous is football? Lisa McHale, widow of Tom McHale, said, "What's even more disturbing to me, and the reason I am here, is that Tom is not alone. His is now the sixth confirmed case of CTE among former professional football players. Bearing in mind that only six former players, over the age of 25, have been tested for CTE, I find these results to be not only incredibly significant, but profoundly disturbing. And I just can't conceive of anyone Science News ... from universities, journals, and other research organizations SaveEmailPrintShare Football And Progressive Brain Damage: Tom McHale Of NFL Suffered From Chronic Traumatic Encephalopathy When He Died In 2008 ScienceDaily (Jan. 27, 2009)— Leading medical experts at the Center for the Study of Traumatic Encephalopathy (CSTE) at Boston University School of Medicine (BUSM) reported today that nine-year NFL veteran, former Tampa Bay Buccaneer Tom McHale was suffering from chronic traumatic encephalopathy (CTE), a degenerative brain disease caused by head trauma, when he died in 2008 at the age of 45. • See Also: • Health & Medicine • Alzheimer's Research • Healthy Aging • Brain Tumor • Mind & Brain • Brain Injury • Dementia • Alzheimer's • Reference • Encephalopathy • Dementia with Lewy bodies • Brain damage • Amnesia • In addition, the CSTE has discovered early evidence of CTE in the youngest case to date, a recently deceased 18-year-old boy who suffered multiple concussions in high school football. • McHale, a Cornell University graduate, former restaurateur, husband and father of three boys, is the sixth former NFL player to be diagnosed post-mortem with CTE since 2002. CTE, a progressive neurodegenerative disease caused by repetitive trauma to the brain, is characterized by the build-up of a toxic protein called tau in the form of neurofibrillary tangles (NFTs) and neuropil threads (NTs) throughout the brain. The abnormal protein initially impairs the normal functioning of the brain and eventually kills brain cells. Early on, CTE sufferers may display clinical symptoms such as memory impairment, emotional instability, erratic behavior, depression and problems with impulse control. However, CTE eventually progresses to full-blown dementia. McHale died due to a drug overdose after a multi-year battle with addiction. Expert consensus is that drug abuse of any kind would never cause the neuropathological findings of CTE seen in McHale. • The other former NFL players diagnosed with CTE are former Pittsburgh Steelers Mike Webster, Terry Long and Justin Strzelczyk, along with Andre Waters and John Grimsley. Waters and Long committed suicide. Grimsley, an avid and experienced gunsman, died in 2008 from a self-inflicted gunshot wound that the medical examiner ruled as accidental. All six NFL CTE sufferers died by the age of 50. Damien Nash, who died in 2007 at the age of 24, is the only former NFL player to be examined neuropathologically and not have CTE. Chris Nowinski, co-founder of the non-profit Sports Legacy Institute (SLI), explained, "This means that six of six deceased former NFL players between the ages of 25 and 50 have had severe brain damage that, if they had lived, would have developed into debilitating dementia." • According to Ann McKee, MD, CSTE co-director and a leading neuropathologist who specializes in degenerative brain diseases, "CTE has been described for approximately 80 years. Initially referred to as dementia pugilistica because of the boxers that were originally studied, CTE is now being seen in other athletes. Although the neuropathological findings of CTE are, in some ways, similar to those we see in Alzheimer's disease, they represent a distinct disease with a distinct cause, namely repetitive head trauma." McKee conducted the neuropathological analysis on the brains of both Grimsley and McHale. Her findings of significant CTE in their brains were independently confirmed by E. Tessa Hedley-Whyte, MD, professor of pathology at Harvard Medical School and a neuropathologist at Massachusetts General Hospital. • Due to the growing strength of these findings linking brain trauma on the football field to CTE, a number of living former NFL players have recently agreed to join three-time Super Bowl champion Ted Johnson and seven other former NFL players to donate their brains to Boston University School of Medicine upon death. The new donors include three members of the NFL's 88 Plan, joining Ralph Wenzel, another 88 Plan donor. • The 88 Plan was named after former NFL star John Mackey's jersey number. Mackey, a Hall of Fame tight end for the Colts in the 1960s and 70s, suffers from severe dementia. The plan was created by the NFL to provide families of former players who suffer from some form of dementia with money to support their care. Members of the Plan, by definition, have been diagnosed with "dementia," which refers to progressive memory and cognitive deficits significant enough to impair daily living. During life, it is not possible to determine the underlying disease which causes dementia. • Following death, CSTE doctors will be able verify with certainty whether or not 88 Plan members' dementia was caused by trauma sustained in sports like football (i.e., CTE) or by other causes of dementia, such as Alzheimer's disease. Eleanor Perfetto, PhD, wife of retired NFL player and 88 Plan member, Ralph Wenzel, who served as offensive lineman for the Chargers and Steelers, 1966-73, said, "My husband suffered numerous concussions and other head traumas while playing football and is now exhibiting significant dementia, is living in a locked assisted living facility, and is unable to feed himself or even recall his days playing football. Something needs to be done to prevent this type of tragedy from occurring to other players and their families." • CSTE is a collaboration between SLI and BUSM. SLI was founded by former Harvard football player and WWE pro wrestler Chris Nowinski, and neurosurgeon and concussion expert Robert Cantu, MD, chief of Neurosurgery and director of Sports Medicine at Emerson Hospital in Concord, Mass, and clinical professor Neurosurgery at BUSM. The work at BUSM is being led by McKee, an associate professor of Neurology and Pathology, director of the Neuropathology Core of the BU Alzheimer's Disease Center, and the director of the brain banks of the Framingham Heart Study and the Bedford VA Medical Center, and Robert Stern, PhD, associate professor of Neurology and co-director of the BUSM Alzheimer's Disease Clinical and Research Program. The CSTE received initial funding for their research from BUSM and subsequently received a $100,000 grant from the National Institute on Aging to support their work. This past week, the group of researchers learned that they received a $250,000 grant from the National Operating Committee on Standards for Athletic Equipment (NOCSAE). • Co-Director of the CSTE, Stern, said, "CTE is the only fully preventable cause of dementia. By studying large numbers of athletes throughout their lives, as well as examining brain tissue through our expanding CSTE brain bank, we will be able to determine the specific risk factors for CTE. This, in turn, will foster education and allow meaningful guidelines to be implemented at all levels of athletic participation, from youth, to college, to pro. In the mean time, however, we already know that return to play too soon after a concussion can have devastating results." • The discovery of the initial stages of CTE in an 18-year-old should move the discussion of football's concussion crisis toward youth football. The identity of the 18-year-old will not be revealed at the family's request. According to Cantu who wrote the first return-to-play guidelines, "Our efforts to educate athletes, coaches, and parents on the need to identify and rest concussions have only been moderately successful because people have been willing to look the other way when a child suffers a concussion. I hope the discovery of CTE in a child creates the urgency this issue needs. It is morally and ethically wrong to allow our children to voluntarily suffer this kind of brain trauma without taking the simple educational steps needed to protect them." • Lisa McHale, widow of Tom McHale, said, "What's even more disturbing to me, and the reason I am here, is that Tom is not alone. His is now the sixth confirmed case of CTE among former professional football players. Bearing in mind that only six former players, over the age of 25, have been tested for CTE, I find these results to be not only incredibly significant, but profoundly disturbing. And I just can't conceive of anyone thinking otherwise. I have 9 and 11-year-old boys who are just beginning to play Pop Warner football. In light of Tom's situation and the findings on the high school football player with the initial evidence of CTE, I now question their involvement in a sport that had been so important in our lives." • NFL players who have recently chosen to join the CSTE brain donation registry include Hall of Famers Joe DeLamielleure and Willie Wood, an 88 Plan member. They are joined by Ken Gray, Brent Boyd, Dan Pastorini, Mel Owens, and Chad Levitt, as well as 88 Plan members Wayne Hawkins and Willie Daniel. SLI president and CSTE co-director Nowinski said, "We appreciate the growing support among former NFL players and their choice to give back to past, current, and future generations of athletes. I hope this research serves as a wake-up call that radical change is needed in football to protect the millions of children playing the game." • Share this story on Facebook, Twitter, and Google: • Other social bookmarking and sharing tools: • Share on bloggerShare on diggShare on farkShare on linkedinShare on myspaceShare on newsvineShare on redditShare on stumbleupon|121 Story Source: The above story is reprinted from materials provided by Boston University. Note: Materials may be edited for content and length. For further information, please contact the source cited above.

7. Signs and Symptoms of Dementia Pugilistica • Declining mental ability • Tremors • Rigidity • Bradykinesia • Lack of coordination • Evolution is insidious • Language difficulties

8. Contusion Reyes ‘07

9. Diffuse Axonal Injury

10. Dementia Pugilistica and Parkinson’s Disease • Pallor of substantia nigra (SN) • neuronal loss in SN • Lewy bodies • Tremors • Rigidity • Bradykinesia • Postural instability Pale Normal Pale SN Lewy Bodies

11. Similarities Between Dementia Pugilistica and Alzheimer’s Disease • Progressive dementia • Large numbers of NFTs and NPs • Acetylcholine deficiency • Lesions are usually concentrated in the hippocampus and other parts of the limbic system which are important in memory-related processes, emotional expression and behavior

12. Chronic Traumatic Encephalopathy (CTE) • Latent complication of traumatic brain injury • Neurodegenerative Disorder • Affects young adults and middle aged • Contact sports • Subconcussive and concussive injury • Cognitive and behavioral symptoms • ? Pathophysiology • No treatment

14. Neuropathology of CTE • Lagre numbers of NFT • NFT distribution distinct from AD • May have neuritic plaques

15. Neuronal Morphology and Physiology • Influenced by cytoskeletal proteins • Skeletal scaffolding • Microtubules main cytoskeletal component • Normal neuronal morphology and physiology require stable microtubules

16. Military Servicemen/Women •Non penetrating injuries • Symptoms similar to CTE • High incidence of ALS • High incidence of PTSD • Several thousands affected • Young members of the military

17. Hypotheses • Single/Repeated axonal damage • Biochemical, structural, membrane, and metabolic perturbations • Hyperphosphorylation of tau • Increase NFTs

18. Traumatic Brain Injury (TBI) • Shearing, deformation, elongation and stretching of axons • Alters membrane permeability • Ionic shifts • Caspase and caspain release • Tau phosphorylation, protein misfolding, • truncation, aggregation, cytoskeletal dissolution • * CCI Txg -↑ tau after 24 hrs – 7 days