Preface to the science behind chronic traumatic encephalopathy (CTE).
Prior to writing this article, I spoke extensively with family and friends about the subject matter (concussion movie & chronic traumatic encephalopathy) and it became apparent that I only created more questions in my failed attempt to educate them. The question I heard the most was how can you write about a movie that you haven’t seen? My answer is it’s the same as reading a book before you watch the movie. You know the main points of the story but some details have been changed to enrich the plot. “Concussion” isn’t even the first time this story has been told. In 2013, Frontline aired a documentary on the same subject matter as “Concussion”, titled “League of Denial”. Thus my poor attempt to create a title designed to increase search engine optimization and even worse attempt of a clever pun. The biggest bombshell in regards to the real life story that inspired “Concussion” is that the movie is not actually about concussions. I understand that might be perplexing to some as it is the equivalent of purchasing a ticket to see “Star Wars: The Force Awakens” and then watching “The Martian”. Both stories have the same underlying story line (space); however, the subject matter is quite different. In actuality, Ridley Scott should have title his movie chronic traumatic encephalopathy (CTE). However, I’m guessing having a film titled chronic traumatic encephalopathy (CTE) would not be as big of a draw at the box office. Plus chronic traumatic encephalopathy is not the easiest thing to say. The final question I was asked was aren’t you happy that “Concussion” is generating so much attention about a subject that affects on average 220,000 Canadians each year? Yes and no. It’s great if more people become educated and aware about concussions. Studies have shown that our current management of concussed athletes is not sufficient, as the majority of individuals return to participation prematurely after being cleared by their medical doctor. This has potentially fatal consequences as was the case with Rowan Stringer. Rowan was an Ottawa based high school rugby player that died after suffering multiple concussions in short time span (second impact syndrome). As a result of her death, the Ontario government is voting on whether or not to pass concussion legislation – Rowan’s Law. Making Ontario the first province to do so for concussions, as well as making concussions the only sports injury legislated by the government in Canada. Increased concussion awareness and education is the only reason this legislation ever made it to queens park in the first place. But remember “Concussion” is really about CTE, a subject that I have addressed ad nauseam in this post. For those individuals who do not wish to read 8 pages on CTE I have included summarizes after each chapter. Enjoy!
“Concussion”, a movie with a misleading title about NFL athletes with brain injuries playing in a “League of Denial”
Concussion is the story of Dr. Bennet Omalu played by Will Smith. Dr. Omalu is a forensic neuropathologist from Nigeria who was the first to publish findings comparing NFL players and chronic traumatic encephalopathy (CTE). Dr. Omalu made his discovery when he examined the brain of former NFL star Mike Webster. Webster, nicknamed “Iron Mike” was an offensive linesman and played in the NFL from 1974 until 1990. He was inducted in the Pro Football Hall of Fame In 1997. His career accolades include 4 Super Bowls, 9 Pro Bowl selections, selection to the NFL 75th anniversary all-time team, NFL 1980’s all-decade team, NFL 1970’s all-decade. It is no surprise given his long list of accomplishments that Mike is regarded by some as the best center in NFL history.
As impressive as Mike Webster was on the field, it’s the events that transpired after his career that are the foundations for Ridley Scott’s “Concussion”. Mike suffered from amnesia, dementia, depression and chronic pain. He also began to distance himself from loved ones and spent a significant portion of his retirement living out of his pickup truck or staying in train stations. In his final years, Mike stayed with his youngest son, who had to act like a parent to Mike even though he was still a teenager. Having suffered enough watching the man she loved self-destruct, Pamela Webster divorced Mike six months before his death in 2002. Mike Webster was 50 years old when died of a heart attack.
What is Chronic traumatic encephalopathy (CTE)
CTE was initially a syndrome that was exclusive to boxers and was coined “punch drunk” or dementia pugilistica. Research from Dr. Omalu and other has lead to a revision or modern definition of CTE. The only difference between the school of thought of Dr. Omalu and his colleagues is that Dr. Omalu states that CTE can be caused by one impact where as other researchers have stated that multiple impacts are required. According to Dr. Omalu and other researchers, CTE has a strong environmental component where concussive (impacts causing concussions) and subconcussive (impacts not causing concussions) injuries cause alterations to the brain that manifest within 8 to 10 years after retirement from contact sports. These neuropathic (brain) alterations are exhibited in changes in the individual’s behavioral and cognitive abilities. The important caveat to mention is the diagnosis of CTE is made post-mortem (Love et al., 2015). This was the case with Mike Webster where Dr. Omalu discovered neurofibrillary tangles (NFT) and phosphorylated tau proteins in specific regions of his brain. Dr. Omalu associated his discovery of NFT’s and phosphorylated tau proteins to Mike Webster’s documented behavioral and cognitive impairments.
What Causes (Pathophysiology) Chronic Traumatic Encephalopathy (CTE)
Bear with me for the next paragraph because it’s going to get technical as I try to describe tau proteins and NFT’s. Or you can skip this paragraph completely and just trust me when I say the modern definition of CTE relies on post-mortem analysis of phosphorylated tau protein deposition and NFT aggregation in the brain. Currently there are 20 known neuropathologic conditions associated with abnormal tau protein phosphorylation aggregation in the brain. Tau proteins are located inside the cells of the brain and are responsible for fortifying proteins. Proponents of the modern definition of CTE state that blows to the head cause phosphorylation [addition of a phosphoryl group (PO32−, turn proteins on/off)] of tau proteins to be deposited (Love et al., 2015). It should be noted that research has not substantiated this claim, and it is currently unknown if repeated blows to the head cause phosphorylated tau deposition (Maroon et al., 2015). The deposited phosphorylated tau proteins can aggregate together to form the NFT’s (Love et al., 2015). Previous studies have shown that the presence of tau proteins is an indicator of Alzheimer’s disease. Researchers like Dr. Omalu are trying to prove that post-mortem detection of phosphorylated tau protein deposition and NFT are a hallmark of a modern definition of CTE. So what does the research say?
Opponents of Chronic Traumatic Encephalopathy (CTE)
It should be noted that not all researchers agree with Dr. Omalu’s modern definition of CTE. A paper by Randolph et al, challenged the notion of CTE as a syndrome and concluded that there is no established consensus or scientific clinical/neuropathologic (disease/injury of the brain) criteria for diagnosing CTE. The paper went on to say there is also no controlled epidemiological (study of how often diseases occurs in different groups of people and why) data related to CTE. Research has been unable to show whether or not repeated hits to the head cause CTE (phosphorylated tau deposition) (Maroon et al., 2015). The authors concluded that based on clinical studies of cognitively impaired retired professional football players; there is no clinical syndrome unique to CTE (Love et al., 2015).
Location and levels of tau proteins in chronic traumatic encephalopathy (CTE) specimens
A paper by Puvenna et al., 2015, compared 6 post-mortem CTE brains with 19 patients diagnosed with temporal lobe epilepsy (TLE) (no history of concussions) who had a portion of their brain (temporal lobe) surgically removed. The authors found no difference in the levels of tau proteins between both the CTE and TLE groups; however, both groups had increased levels compared to a normal population. The authors of this study concluded that increased levels of tau deposition may not be specific to repetitive traumatic brain injuries (concussions).
Another study had similar findings to Puvenna at al., 2015, in that tau protein levels where increased in CTE patients compared to a control population; however, there was no difference between CTE and TLE tau protein levels (Prager et al., 2015).
A promising paper by Barrio et al., 2015, showed a distinct and statistically significantly pattern of tau deposits in CTE specimens compared to both Alzheimer’s (AD) patients and healthy individuals. The authors found that tau proteins in CTE specimens were deposited in higher concentrations in cortical and subcortical regions, as well as in deeper structures (amygdala and midbrain). The researchers also noted that as CTE progresses (disease gets worse) phosphorylated tau protein deposition spread from the front of the brain to back as the disease progressed. This presentation is distinct from AD where tau protein deposition was more diffuse and did not have a preference for the front of the brain (anterior cortex).
Even though Barrio et al., 2015 were able to show a distinct pattern of tau protein deposition compared to AD. Puvenna et al (2015), found that the phosphorylation site-specific tau proteins thought to be characteristic of CTE patients were also present in patients with temporal lobe epilepsy, as well as a few healthy subjects.
Summary about the location and levels of tau proteins in chronic traumatic encephalopathy (CTE) specimens:
Measurement of tau protein levels is not a specific means of diagnosing CTE, as individuals with TLE had similar increases of tau protein levels. Research has shown that as CTE progresses in severity, tau protein deposition migrates from the front of the brain to back. The same researchers also found that CTE patients have a unique pattern of tau protein deposition compared to Alzheimer patients. However, other researchers have demonstrated that CTE does not have a distinctive site-specific tau protein deposition. Puvenna et al (2015), showed that tau protein site-specific deposition was similar in CTE, TLE and even some healthy individuals. Therefore, tau protein levels and site-specific phosphorylated tau protein depositions are not a reliable means of diagnosing CTE in post-mortem specimens.
Even if tau protein levels and site-specific tau depositions were a reliable means of diagnosing CTE – remember they’re not – these findings do not correspond with increased neurological deficits. One of the key proponents of CTE (Dr. McKee) reported that 11% of post-mortem diagnosed CTE individuals did not have a history of behavioral or cognitive impairments. This was true in even some cases with an advanced stage CTE diagnosed post-mortem.
Chronic traumatic encephalopathy (CTE) and Prior Exposure to Contact Sports
One of the largest published studies on CTE utilized the Mayo clinic brain bank for neurodegenerative disorders. It should be noted the brain bank was setup for all neurodegenerative disorders, not just specifically CTE. The study examined 1721 male brains. Researchers checked the medical records of the deceased individuals to see if they had participated in contact sports. There are some obvious limitations to this methodology; nevertheless, of the 1721 specimens 66 patients had a documented history of exposure to contact sports. The researchers compared the 66 documented cases of previous exposure to contact sports to a control population of 198 individuals with a documented history of no previous exposure to contact sports. It is important to state that of the 198 specimens, 33 individuals had a documented single-incident of traumatic brain injury (concussion or more serious brain injury) due to a fall, motor vehicle accident or other cause not related to contact sports. The article found that 21 of the 66 former athletes had pathology consistent with CTE (Bieniek et al., 2015). It should be noted that there have only been 153 documented cases of CTE in scientific literature (Maroon et al., 2015). The researchers also found that none of the individuals in the control group had CTE pathology. The authors concluded that the greatest risk factor for diagnosed CTE (post-mortem) was exposure to contact sports (Bieniek et al., 2015).
Summary of chronic traumatic encephalopathy (CTE) and prior exposure to contact sports:
If exposure to contact sports resulted in a 1/3 of the population developing CTE pathology, then you would expect to see the same representation in the group of 33 individuals with a documented single-incident TBI (concussion or more serious brain injury). Remember that Dr. Omalu position states that CTE can develop as a result of a single impact. However, as the authors stated none of the 33 individuals had pathology consistent with CTE. It is a possibility that the 21 former athletes may have suffered numerous impacts (concussions) within a shorten time frame. This is referred to as a second impact syndrome and studies have shown that 10-15% of concussed individuals experience this – think Sidney Crosby. A concussion is a functional brain injury that causes an energy deficit that normalizes in approximately 30 days. If an athlete experiences a second concussion before they are fully healed, their energy levels will drop below a minimum threshold that cells in the brain need to survive. This can lead to permanent and irreversible structural changes in the brain causing paralysis and death. It is impossible to know if the 21 former athletes received proper care and management for any injuries they received. Maybe they would not have had pathological evidence of CTE (post-mortem) if they had been properly managed, and would have presented similarly to the 33 individuals with a single-incident TBI.
Chronic traumatic encephalopathy (CTE) and Suicide
Director Ridley Scott’s inspiration for a NFL concussion film came from his investigation into the deaths of other former NFL stars Junior Seau and Dave Duerson. Sadly both individuals committed suicide and were diagnosed with CTE (post-mortem). Increased suicidal tendency is a major proposed clinical feature of CTE; however, what does the literature say?
Suicide was not mentioned as a clinical feature of CTE in any published literature between 1928 and 2009. It wasn’t until 2010 that the correlation of suicide and CTE began to be published in research papers. One of the reasons why it wasn’t published was that between 1960 and 2007 there were only 9 reported suicides of former NFL players. That rate is half of the incidences of suicide in U.S males of the same age. However, 2012 was a dark year for the NFL as 6 of their current and former athletes committed suicide. This obviously received a lot of attention in the media. Numerous studies were published correlating contact sports with concussive/subconcussive impacts to an increased risk of CTE, and that CTE lead to behavioral changes that included increased suicidal tendencies. However, is there another possible explanation for the drastic increase of suicides among NFL athletes?
The risk factors for suicide include financial difficulties, substance abuse, conflicts/problems with family members or significant others, limited social connectedness, chronic pain, hopelessness, impulsivity/aggression and physical illness & poor general health. It should be noted that a recent anonymous survey of 763 retired NFL players found that 61% had difficulty adjusting to life after football, 51% were struggling financially, 48% experienced marital difficulties, 34% had difficulty finding employment, 31% were depressed and 27% took prescription painkillers (Iverson et al., 2015). Another study found that retired NFL players have depression rates consistent with the general population (Solomon et al., 2015).
As mentioned previously one of the major risk factors for suicide is substance abuse. A study investigating CTE and substance abuse found that only 30 CTE specimens had a documented history of substance abuse (Maroon et al., 2015). Substance abuse included alcohol, prescription painkillers, steroids, cocaine, methamphetamines, and marijuana. However, this number might be underrepresented as family members were often the ones interviewed post-mortem and might have been unaware of substance abuse problems. Furthermore, previous studies have shown rampant substance abuse among NFL players.
Summary about chronic traumatic encephalopathy (CTE) and Suicide:
The increased prevalence of suicides documented in 2012 can be attributed to the difficulties professional athletes experience when they retire. Also, even taking into account the recent spike of suicides, active/retired NFL players are still at a lower risk for suicide than the general population. Furthermore, research has not established that tau pathology causes complex changes in behavior such as depression, substance abuse, suicidal tendencies, personality changes or cognitive impairment. Remember, 11% of diagnosed CTE individuals (even some with advanced stage CTE progression) had no documented behavioral or cognitive impairments (McKee et al). Furthermore, the prevalence of suicide and accidental death is higher in individuals with less advanced stages of CTE (Iverson et al., 2015). This suggests that increased suicidal tendencies may be a result of other existing factors – such as the ones mentioned previously, and not an association with CTE progression. Remember Mike Webster? Even though he did not commit suicide he still suffered from amnesia, dementia, depression, chronic pain, had marital difficulties, struggled financially and had trouble adjusting to life after football. There were also unconfirmed reports that Mike used anabolic steroids during his career. Mike never admitted to using steroids but did state that if he did take performance enhancing drugs. “they were legal at the time”.
Age and Cause of Death in Chronic Traumatic Encephalopathy (CTE) Individuals
One of the diagnostic criteria of CTE is that there are behavior and cognitive impairments that present 8-10 years after retirement from contact sports. A study by Maroon et al, 2015, looked at the age and causes of death in 150 CTE diagnosed individuals. The age of death in CTE diagnosed individuals ranged from 17 to 98 years of age. The breakdown of deaths per decade were as follows: 3 (10-19), 16 (20-29), 9 (30-39), 21 (40-49), 21 (50-59), 39* (60-69), 26 (70-79), 12 (80-89) and 3 (90-99). The median age of death of 60-69 is lower than the average U.S population. The authors found no relationship between CTE and the age of death as almost every decade had at least one diagnosed case of CTE (Maroon et al., 2015).
The same authors then looked at the cause of death in CTE diagnosed individuals. They were able to identify the cause of death in 111 cases. Of all the documented cases not one cause of death was attributed to CTE. The most common cause of death among post-mortem CTE diagnosed individuals was natural causes [78 cases (respiratory failure, cardiac disease, cancer, etc.)]. The other attributed causes of death were accidental [19 (drug overdose and severe traumatic brain injury) and suicide (14 cases).
Summary about chronic traumatic encephalopathy (CTE) and cause/age of death:
There is no relationship between CTE and the age of death. The median age of deaths in CTE cases is lower than the general public; however, this can partially be attributed to the increased prevalence of accidental death and to some extent suicide in this age demographic. Remember there might be other co-founding factors for the suicide rate among CTE individuals. Also, due to the limited data the natural progression of CTE is unknown. Larger studies are needed to demonstrate whether or not CTE diagnosed in younger individuals would progress to advanced behavioral or cognitive impairments. Dr. Omalu stated in 2011 that caution should be exercised when diagnosing CTE in individuals over 65. This is because normal ageing, Alzheimer’s disease, chronic ischemic conditions and small vessel disease can all change the structure of the brain. This can cause confusion in regards to which pathological changes in the brain were related to CTE.
Appraisal of Chronic Traumatic Encephalopathy (CTE) Research
Most of the studies written on (CTE) have been shown to have a large selection bias. This is due to an increased CTE reporting among high-profile, former NFL players who have committed suicide or died of natural causes. This increased reporting of big name players may also contribute to an overestimation of CTE-related deaths. Studies have shown that individuals and family members of deceased former NFL players who have died as a result of suicides or natural causes are disproportionately more likely to participate in CTE brain donor programs. This can skew the incidences of CTE, as a former NFL player or their family members may be more inclined to donate to brain donor program compared to a non-professional athlete who also has a prior history of exposure to contact sports.
Furthermore, the documented behavioral and cognitive impairments in chronic traumatic encephalopathy (CTE) individuals are usually presented to the researchers by the deceased next of kin. There is an obvious bias here as family members may omit or be unaware of certain details. Also, there is a known phenomenon, “good old days syndrome”, among family members of concussed individuals. This is where family members attribute an event that a concussed individual has always done – forgetting where you put your keys, losing your wallet – as a side effect of a concussion. It is a possibility that some of the cognitive impairments documented by family members of CTE individuals could be attributed to the “good old days syndrome”.
Finally, most of the research presented on chronic traumatic encephalopathy (CTE) involves case-series & case-reports. These types of studies can be beneficial but are not the most rigorous when it comes to empirical research. There has yet to be a large, longitudinal study conducted to substantiate the prevalence of CTE. Also, the estimated number of former participants in contact sports and military combat with a reported history of a concussion is estimated to be in the millions. A recent paper extrapolated the annual incidence of concussions in Canada to be approximately 220,000. To accurately determine the actual incidence and prevalence of CTE would require thousands of participants over the span of decades (Maroon et al., 2015). To summarize better studies over a longer period of time are needed.
Chronic Traumatic Encephalopathy (CTE) and Advice for Parents
Any film or media outlet that raises awareness about a serious condition is a step in a positive direction. Nevertheless, it is imperative that those who are in charge of the narrative do so in a manner that is an unbiased representation of all of the available material. Obviously, this will never happen in a movie because the end product would not be as thrilling. Hollywood movies are fun to watch in the theatre, but when it comes to a serious healthcare condition the general public needs to be properly informed.
There is also a chance that parents and athletes alike might not want to participate in sports due to a limited knowledge about concussions and potential long term side effects (CTE). According to the US Census Bureau for sport’s participation, tackle football enrollment rates decreased by 13 percent from 2011 to 2012 and most notably among players 7 to 11 years old. There are a number of reasons that can be attributed to the decline of adolescents in tackle football. Nevertheless, one of the most cited reasons is the potential long term effects of concussions (CTE) and other traumatic brain injuries. This past summer, San Francisco 49ers linebacker and one of the top rookies of the year Chris Borland decided to retire from professional football. When asked in an interview with ESPN why he decided to retire so early into a promising career? Chris responded that he had done a lot of research and had concerns about the long-term effects of repetitive head trauma. Chris Borland even cited stories of other former NFL players; such as, Mike Webster and Dave Duerson and how their tragic deaths influenced his decision.
There has been a lot of media attention recently in regards to concussions and chronic traumatic encephalopathy (CTE) – “Concussion” and “League of Denial”; however, like most subjects more research and better studies are needed. It is also important that independent documentaries present an accurate depiction of the literature, so that parents and athletes can make an informed decision about their well being. Minor sports organizations need to be willing to adopt new policy and rule changes making player safety paramount above all else. Finally, as a society we must educate coaches, parents, trainers and athletes about concussions and ensure that proper management – baseline testing and return to learn/play protocols – is followed.
For more information on concussions or CTE please visit sportsrehabandwellness.ca or completeconcussions.com.