cte: what we don’t know

Sunday, July 31, 2016

The press has not been kind to Gary Bettman this week and this time, the press is wrong. The NHL Commissioner wrote a letter in response to questions asked by Connecticut Senator, Richard Blumenthal, that outlined the league’s position regarding concussion and the long term effects of head injury. The New York Times called out his “reluctance to link hits to the head in hockey with a degenerative brain disease”.  Sports Illustrated wrote of the “refusal to acknowledge a possible link between concussions and CTE has proved to be controversial.”

“I was surprised and appalled, because I thought the response would be more receptive,” Blumenthal told SI.com via telephone from Philadelphia. “I would’ve welcomed an acknowledgement for stronger action and a commitment to determining whether the game is causing these heartrending injuries with such painful consequences, rather than dismissing the link between hockey and CTE.” 

Mr. Bettman’s 24-page letter acknowledged the potential for head injury and concussion in all contact sports and also summarized the medical literature that has yet to prove that chronic traumatic encephalopathy (CTE) is caused by concussion. While it seems intuitive that CTE is caused by trauma, there are major questions that remain unanswered.

Association v. Causation

There is no doubt that there is an association between traumatic brain injury and CTE, but the research is just beginning as to what causes some people to develop CTE and others to be spared. Or have they been? With todays’ science and technology, CTE can only be diagnosed after death by autopsy, and then only if the brain is dissected and special stains are used to look at cells under the microscope. Of the athletes whose brains have been studied, there seems to be a correlation between the many concussions that they had sustained and CTE findings in the lab. Unfortunately, there is a problem with the statistics.

For a cause and effect to be found, brains from different groups of athletes need to be studied:

  • Those who had no concussion history and no signs or symptoms of depression or dementia
  • Those who had no concussion history but developed signs or symptoms of depression or dementia
  • Those who had a concussion history and had no signs or symptoms of depression or dementia.

As of now, researchers have mostly studied those who have had a history of concussion and developed signs of mental illness and/or dementia.

What do we know?

There is evidence that there is a link exists between a severe traumatic brain injury and the eventual development of dementia. There also may be a dose relationship, meaning the more severe the head injury, the more likely dementia becomes a future possibility.  However, there is not necessarily that same link that connects repetitive minor head injuries with CTE. Lots of small concussions does not necessarily equal one major head injury.

…specifically for rTBI (recurrent mild traumatic brain injury), there has been an unavoidable case-selection bias and a virtual absence of control material from uninjured cases in reports of CTE, rendering interpretations of the incidence of this pathology meaningless in the context of exposure to repetitive mild injury. –  Hay J, et al. Annual Review of Pathology. May 2016

While the public is hearing about brain chemistry and anatomy, including tau proteins and neurofibrillary tangles, other research is ongoing looking at other markers of brain injury. These include amyloid deposits, DNA binding proteins, neuroinflammtion, brain white matter degradation and neuron (brain cell) loss. Chromosome research may offer some clues to CTE development, with certain genes more likely to be associated  CTE after a brain injury and others that might injure the brain by activating certain enzymes. 

What don’t we know?

Traumatic brain injury is known to be the biggest risk factor for developing dementia. The question is how much brain trauma is needed to cause CTE.

  • Does it take one or multiple concussions?
  • Are concussions spaced closer together more dangerous? Or does the same damage occur even when they are spaced years apart.
  • Is concussion in children and teenagers more important than later in life? or are their brains better able to adapt and heal themselves?
  • Do brains heal themselves and become pristine after a period of time, or is the concussion damage permanent?
  • Why do some concussion patients develop depression and dementia, while other do not?

The bottom line is that while a relationship exists between head injury and degenerative brain disease, scientific research has yet to prove that concussion causes CTE. There are many next steps for research to take, including being able to diagnose CTE in live patients without having to wait until they die to perform an autopsy. For now, we know that we don’t know a lot.

There are known knowns. These are things we know that we know. There are known unknowns. That is to say, there are things that we know we don’t know. But there are also unknown unknowns. There are things we don’t know we don’t know. – Donald Rumsfeld.


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CTE: what we don’t know

Sunday, May 24, 2015

There is danger in learning medicine by assertions published by the press, and there is risk in relying upon isolated extracted quotes that may or may not reflect an expert’s view. It is especially difficult when the science behind a theory is very new. Changes in medical knowledge happen slowly and early adopters of new theories are often proven wrong…or are driven to develop compelling research that makes a difference in how medical care is provided.

All this to talk about chronic traumatic encephalopathy (CTE) and the criticism of Gary Bettman, NHL commissioner, when he was suggested in a press conference, that the correlation between head trauma and CTE has yet to be proven.

From a medical science standpoint, there is no evidence yet that one (concussion) necessarily leads to the other (CTE),” said Bettman to reporters on hand. “I know there are a lot of theories, but if you ask people who study it, they tell you there is no statistical correlation that can definitively make that conclusion.

Mr. Bettman was taken to task by researchers, broadcasters and others who want to be able to explain the consequences of repetitive head injuries, and how to prevent concussions in sports, the military and other workplaces, from causing significant brain deterioration, and loss of mental function and early death.

Chris Nowinski, the executive director and co-founder of the Sports Legacy Institute an also works with the Boston University CTE Center, was quoted by Josh Cooper of Yahoo Sports:

We have plenty of medical and scientific evidence that brain trauma leads to CTE. In fact the experts from the Department of Defense and the National Institute of Health are both on record saying they personally believe that CTE is caused by brain trauma.

Ray Slover of the Chicago Tribune wrote the following:

Gary Bettman might have been speaking as a lawyer as well as head of the National Hockey League this week when he said there was no established link between concussions and chronic traumatic encephalopathy.

He also might have been the NHL equivalent of an ostrich sticking his head in the sand or a climate-change denier. Bettman’s stand certainly seems to fly in the face of medical evidence.

Keith Olbermann named Mr. Bettman the worst person in the sports world on his May 22, 2015 television program.

For all this rhetoric, perhaps it’s important to take a step back and try to acknowledge that we know only what we know. Perhaps we should turn to the experts for their understanding of CTE and its causes. This is a relatively new disease entity, so new in fact, that there was not a standardized set of criteria to make the diagnosis. In February 2015, a consensus conference was held by the National Institutes of Health. The diagnosis can only be made at autopsy, when abnormal tau proteins are found irregularly scattered within the depths of brain tissue and cells. The abnormal protein “pathology has only been found in individuals exposed to brain trauma, typically multiple episodes.  How common this pathology occurs at autopsy and the nature and degree of trauma necessary to cause this neurodegeneration remain to be determined.”

The “to be determined” is a big step for science when it comes to cause and effect. In the presentation of the group’s consensus, Dr. Ann McKee, of the CTE Center, wrote the following bullet points:

“Relationship between concussion, subconcussion and CTE is unclear”

  • Concussion, subconcussion and post-concussion syndrome: most likely reversible states of neuronal and axonal derangement
  • CTE- a latent, progressive neurodegenerative disease.
  • Repetitive injury superimposed on unresolved injury may initiate a series of metabolic and cytoskeletal disturbances that trigger a pathological cascade leading to CTE in susceptible individuals
  • The number of concussions does not correlate with CTE or predict CTE
  • However, the severity of CTE is significantly associated with length of exposure in American football, and it is likely that this is a result of the cumulative effects of subconcussive injury

There is still much work to be done to build on the initial finding of the CTE group. Many more brains need to be analyzed, since a sampling bias needs to be removed from the research. The brain banks that accept tissue donated from athletes and their families who suspect that a major neurologic problem exist. This may skew what might be happening in the general population. Many people have minor head injuries and perhaps the Tau deposition is more commonly spread throughout the population than presently known. The special pathology tests are not routinely done on every autopsy, but the deposits of tau protein in CTE differs than the same protein distribution in Alzheimer’s Disease. Volunteers from the general public are being recruited to keep diaries of their lives and donate their brains science. This will not be a short term project.

A great doctor or scientist knows what they know and what they don’t. It is hard to pursue the mysteries of the human body. Mr. Bettman reminded us that while we think we might know some answers, there are significant gaps in our understanding of the brain. Head trauma may cause CTE but we don’t know how many are needed, how severe or how often they might occur and what victims are more susceptible to the disease. We do not know how to make the diagnosis when people are alive, nor how to treat them to prevent the development of CTE. And we don’t know how to treat CTE should the symptoms be recognized. The bottom line is that we don’t know very much.





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