ARTICLE IN BRIEF
Postmortem tissue from NFL linebacker John Grimsley showed evidence of chronic traumatic encephalopathy; investigators at Boston University link the condition to his past history of concussions.
Concussion on the heels of other athletic injuries could pave the way for Alzheimer disease (AD) and other cognitive problems, according to growing evidence of chronic traumatic encephalopathy (CTE) in athletes who had sustained multiple injuries to the brain and died prematurely. At autopsy, their brains were riddled with the classic tau-filled tangles that are also seen in AD. These athletes were in their 30s and 40s and had complained of memory loss and behavioral changes that made sense only in death when their brains showed pathological signs of disease and cell death.
The latest brain tissue to go under the microscope in search of abnormal accumulations of tau protein belonged to former National Football League (NFL) player John Grimsley, a linebacker for seven seasons with the Houston Oilers. After Grimsley's accidental death in February 2008, Chris Nowinski, a former Harvard football player and professional wrestler, reached out to Grimsley's wife Virginia to ask whether scientists could study her husband's brain. John Grimsley's wife said yes.
Nowinski started the Sports Legacy Institute in 2007 to bring attention to the serious health issues stemming from repeated concussions. He has approached families of professional athletes in the throes of grieving with a poignant story of brains damaged by repeated concussions that were either undiagnosed or not given time to heal. At 30, Nowinski had several concussions that resulted in cognitive impairments.
NEW REPORT ON CTE
Figure. TAU PROTEIN ...Image Tools
In a phone interview with Neurology Today in September, scientists at Boston University said Grimsley's brain had all the pathological signs of chronic traumatic encephalopathy (CTE). He was 45, and in the last two years had noticeable problems with short-term memory. This finding adds to the mounting evidence that repeated blows to the brain may seem benign but can have a cumulative and devastating effect on the brain, setting in motion a dementia that is generally seen in aging populations.
CTE was first described in the 1920s when doctors described a phenomenon among professional boxers that made them appear “punch-drunk” after many years of repeated blows to the head. Dementia pugilistica has been noted in professional boxers for more than 50 years.
There are two-dozen symptoms of CTE, including memory disturbance, confusion, gait disturbances or falls, speech abnormalities and mood problems.
Autopsies of Grimsley and four other former NFL players who died in their 30s and 40s revealed they had neurofibrillary tangles in neurons and glial cells. Working with the Sports Legacy Institute, University of Pittsburgh neuropathology Bennett Omalu, PhD, of the University of Pittsburgh, had previously found CTE in former NFL players Terry Long, Mike Webster, Andre Waters, and Justin Stzelczyk. Brain tissue from a fifth athlete who died at 24 years old showed no evidence of a tauopathy.
“We didn't expect to see brain damage in this young man,” said Robert Stern, PhD, co-director of the Center for the Study of Traumatic Encephalopathy at Boston University School of Medicine. CTE often requires repeated injuries and it could be a dose effect that would not show up in professional athletes in their early 20s.
Last year, the Center signed a collaborative agreement with the Sports Legacy Institute to study the brains of professional athletes to begin to understand the effects of chronic head trauma and the risk for dementia.
Figure. TAU PROTEIN ...Image Tools
ATHLETE BRAIN BANK
In September, the Center announced the establishment of a brain bank dedicated to studying tissue from professional athletes. So far, a dozen athletes have signed on, including former New England Patriots linebacker Ted Johnson. Johnson, now 35, said that he suffers from memory problems and depression. The former football player had multiple concussions during his years on the field.
“The repeated trauma sets something in motion,” said Robert C. Cantu, MD, a clinical professor of neurosurgery at Boston University School of Medicine, chief of neurosurgery at Emerson Hospital in Massachusetts, and co-founder of the Sports Legacy Institute. Dr. Cantu, an expert on concussion, added: “Unlike injuries to other parts of the body, the consequences of trying to play hurt are huge. Athletes should always allow time for recovery before they go back to playing.”
Grimsley had only one documented concussion but doctors estimate that he may have had eight others.
Ann McKee, MD, director of neuropathology at the Boston University Alzheimer's Disease Center, did the pathological assessment of Grimsley's brain, including immunohistochemistry to look for tau deposition. And there it was, spread out over the frontal cortex, amygdala, and just about everywhere they looked.
The neuropathological diagnosis of CTE was confirmed independently by E. Tessa Hedley-Whyte, MD, a professor of pathology at Harvard Medical School. Dr. Hedley-Whyte did not know the age or the profession of the man whose brain slices were sent to her for inspection.
The brain donation program will allow scientists to ask questions of professional athletes that will eventually be used in the postmortem analysis. Dr. Stern said the team will ask athletes to participate in studies to test cognitive performance and follow changes over time in the event of repeated concussions. They will also study athletes who have never had a concussion to determine what other factors put people at risk.
Dr. McKee said that the deposition of tau observed in the brains of this handful of athletes provides evidence that acquired injuries can lead to a progressive neurodegenerative disease. She has found similar tauopathies in the brains of four professional boxers.
“There is a tremendous amount of deposition,” said Dr. McKee. “It is not just in the cortex but in white matter as well. Deposition is also seen around the blood vessels.” She suspects that the repeated brain trauma could trigger a breach in the blood-brain-barrier and allow toxins to leak into the brain.
RESPONSE FROM THE NFL
In response to the publicity generated from the Grimsley autopsy, the NFL issued a statement saying that the organization is conducting its own research on the long-term effects of concussion and that findings will be available by 2010. The NFL also held a meeting last June to discuss the research with sports physicians.
Dr. Cantu commends this effort but said that the NFL should have other experts weigh in on their internal investigation on concussion. In 1986, Dr. Cantu issued concussion guidelines for doctors who treat professional athletes. An international committee of experts also published similar guidelines in 2001. The guidelines state that a full recovery is imperative before resuming the sport.
CTE is rare and occurs in those athletes who get injured repeatedly without letting the brain recover. No one knows how tau builds up in the brains of these athletes.
“Athletes who sustain multiple traumas may be okay today but could sustain neurological problems when they are older,” said Barry Jordan, MD, director of the Brain Injury Program at Burke Rehabilitation Hospital and chief medical officer for the New York State Athletic Commission. “It is important to look at the brains of professional athletes in contact and collision sports to see what the pathology is and to begin to learn about the pathophysiology.”
“The key is protecting against acute concussion,” said Dr. Jordan. “And that means understanding what a concussion is and having pre-competition screening and surveillance, proper medical care post injury, and making sure that athletes do not go back into the game before they are healed.”
He supports the push for brain banks for professional athletes but stresses that it would only work if they get accurate information on their history of concussions.
Sam Gandy, MD, PhD, Sinai Professor of Alzheimer's Disease Research, professor of neurology and psychiatry, and associate director of the Mount Sinai Alzheimer's Disease Research Center at Mount Sinai School of Medicine in Manhattan, said that new to the current debate on the long-term consequences of concussion is the notion “that there are molecular cascades of pathogenic changes that can continue inside the concussed brain even after the initial symptoms… subside and the athlete appears normal again.”
This process can accelerate a neurodegenerative process. But all scientists agree that there are other factors that weigh in on this process and an effort is under way to identify these risks help predict and identify those who may be more susceptible to developing CTE and the ensuing tauopathy.
CONCUSSION AND CHRONIC TRAUMATIC ENCEPHALOPATHY
Neurology Today has reported previously on the association between concussion and chronic traumatic encephalopathy. Visit neurotodayonline.com for these articles:
* “Brain Damage May Have Contributed to Former Wrestler's Violent Demise,” Sept. 18, 2007
* “With Fewer Autopsies, Fewer Brains for Research,” Sept. 4, 2007
* “Fourth Case of Chronic Traumatic Encephalopathy Reported in Former FNL Player,” July 17, 2007
* “Football Concussions Linked to Depression, Cognitive Impairment: Experts Seek Prospective Studies,” March 6, 2007