By Anthony B. Corleto and Alia A. Najjar, of Wilson Elsner
The disease known as chronic traumatic encephalopathy (CTE) is detected at autopsy. Using immunohistochemical staining technology, pathologists look for abnormal depositions of hyper-phosphorylated tau protein, a substance that occurs naturally in the body and is responsible for stabilizing nerve cells. If the staining pattern matches certain criteria, a diagnosis is made, such as CTE, Lewy Body disease or Alzheimer’s disease. There are many conditions in which the protein tau accumulates in the brain; it even accumulates with aging.
Much work is being done to correlate postmortem CTE pathology with antemortem behavior and neurological function. A correlation could help us understand and alter activity that puts us at risk. Media focus on CTE has brought public awareness to a subject that might otherwise be relegated to the world of medical literature. Frequently in the spotlight, Dr. Ann McKee and her colleagues at Boston University (BU) should be commended for their work in collecting brains and studying tissue samples, which has potentially large implications.
However, the matter is far from settled in the scientific community.
Background
Dr. McKee and a host of her colleagues published a report, “Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football,” in the Journal of the American Medical Association (JAMA), which was featured in the New York Times piece, “110 out of 111 NFL Brains.” The article paints the picture that any pro football player stands a near certainty of neurological impairment based on CTE. In “0.44% of NFL Brains” Wilson Elser addressed the New York Times coverage and pointed out the study’s limitations.
BU’s 2018 follow-up about “subconcussive” contact got similar media coverage and became the centerpiece of efforts to outlaw organized youth contact sports in a number of states. Pushback from the larger medical community, “limiting head impacts among youth is smart, overstating scientific consensus is not,” and grassroots efforts led by parents, volunteers and youth-serving organizations have at least temporarily halted those legislative efforts. In “The Freedom to Swim” Wilson Elser addressed this study’s limitations, in particular the prevalence of CTE among the general population. We also noted the potential consequence of kids playing unorganized football without the benefit of proper equipment, adult supervision and concussion protocols, and that the sport the very object of which is to deliver a concussion (boxing) doesn’t get the same attention as football.
BU’s latest effort, the age of first exposure (AFE) study, concludes that kids who play tackle football and continue through college or beyond have “earlier neurobehavioral symptom onset,” and that youth exposure to tackle football “may reduce resiliency to late-life neuropathology.” The AFE study looks like a repackaged version of BU’s 2015 piece, which drew conclusions about AFE and later-life cognition in former NFL players. Both studies draw from the same pool of data at the BU Brain Bank. One looked only at subjects reported to have played youth football, while another used the larger universe of BU’s football player subjects (high school, college, professional) without regard to whether they played youth football, the idea being to get a “control” group. Both drew dissent and criticism from the larger medical community.
What does it mean?
The BU reports draw from the same universe of data. None of the BU subjects has been followed or examined by clinicians for these studies. All have been “diagnosed” based on speculative and unreliable next-of-kin reports. None of the BU studies includes a control group; only those who played football at a high level and demonstrated troubling behavior are in the studies. Yet the BU studies correlate exposure to contact sports with life-threatening neurodegenerative disease.
BU’s latest correlation between exposure and disease concludes that those who start playing football below age 14 are more likely to have problems as they age. If true, there are three implications: kids shouldn’t play football, those who did are destined for infirmity, and BU is saving our kids.
One problem with the AFE study is that it makes no association between AFE and severity of CTE pathology. Similar to cancer, BU uses a scale to grade CTE pathology, from mild (Stage I) to severe (Stage IV). Contrary to the narrative, the AFE data actually shows (1) the mild CTE group had double the contact sport participation of the severe CTE group; (2) the CTE-positive group lived longer than the CTE- negative group (62 versus 42); and (3) average age at death in the mild CTE group was earlier than the severe CTE (III/IV) group (49 versus 68). In other words, the experiment doesn’t prove the theory.
Where it began
In 1928, Martland’s groundbreaking study of “Punch Drunk” syndrome looked at boxers who developed neurologic and behavioral issues associated with repeated head trauma. The CTE label was first linked to Punch-Drunk syndrome in the 1940s (“Punch-Drunk syndromes: the chronic traumatic encephalopathy of boxers,” Critchley M., Neuro-chirurgie; hommage à Clovis Vincent, Maloine, Paris: 1949). Since then scientists have tried to identify its implications. Between 1954 and 1967, postmortem studies covered boxers with dementia and Parkinson’s. A 1973 postmortem of 15 boxers with Punch-Drunk syndrome looked at their neuropathology. This work came before the internet and social media. None of it got the attention that today’s studies get.
Fast-forward
In 2005, Bennet Omalu, the Nigerian born pathologist played by Will Smith in Concussion, published the first study associating CTE with professional football. Omalu correlated his 2002 finding of amyloid plaque tau deposits in the brain of Pittsburgh Steeler Mike Webster with family reports of cognitive and behavioral problems. Webster died from coronary artery disease 12 years after retirement.
In 2006, Omalu published a study of Pittsburgh Steeler Terry Long, who committed suicide at 45 by drinking antifreeze. His family reported a first suicide attempt after NFL suspension for steroids, a rollover accident that left him unconscious, a diagnosed major depressive syndrome, hyperthyroidism and a thyroidectomy two months before suicide. Unlike Webster, no amyloid plaque was found. Omalu was unable to account for these and other differences between Long and Webster.
As with the BU reports, neither of the Omalu reports follows their subject antemortem, yet they declare a link between neuropathology and sports concussion.
Where We Are
There remains a scientific gap linking head injuries and neuropathological findings of CTE. In 2015, the National Institutes of Health (NIH) held the first consensus workshop to define neuropathological criteria for the diagnosis of CTE. Despite such attempts to define CTE, there is still no consensus. There is a dearth of research to understand and correlate clinical presentation with postmortem pathology. There is no consensus about the causes of CTE.
There has been no scientific study clearly demonstrating a definitive cause-and-effect relationship between head trauma, development of psychological and behavioral changes later in life, and neurodegenerative changes identified postmortem as CTE.
A recent study showing that CTE may be detected in a living person by PET scan with a tau protein tracer holds some promise, but even its authors admit more research needs to be done. CTE neuropathology has been found in individuals with no psychological or behavioral issues. The inter vivos finding of tauopathy, a class of neurodegenerative diseases associated with the pathological aggregation of tau protein, consistent with CTE in one symptomatic individual still lacks a causal link between pathology and symptoms.
As pointed out in “0.44% of NFL Brains,” the BU studies that retrospectively correlate symptoms with neuropathology cover a select group of athletes known to have sports concussions. Thus, any claim that a percentage of NFL players are at risk for CTE is simply false. The vast majority of NFL players never develop behavioral and cognitive problems attributed to CTE. More than 250,000 men have played in the NFL, and more than 10 million kids have played organized youth football. Rather than focusing on a few select subjects with known outcomes, longitudinal studies look at the bigger picture. True control group studies actually show a prevalence of CTE in the general population equal to or greater than the prevalence among NFL players.
Moving the Ball
The brain is our most important organ and should be protected from unreasonable risk of injury. Media focus and Hollywood depiction based on work from BU and Omalu have helped bring about concussion protocols and better medical management. These are good results.
Aside from a generalized association with disruption of the blood-brain barrier from movement of the brain within the skull, the cause of CTE remains unknown. Until comorbidities such as opioid use and the genetic presence of apolipoprotein-E4 (the major known genetic risk factor for Alzheimer’s disease) are accounted for, the notion that sports participation causes the behavioral and neurological problems attributed by some to CTE remains a theory. Until we account for the prevalence of CTE in the general asymptomatic population, it is unreasonable to assume that simply engaging in sport places one at unreasonable risk of injury.
Disclosures and Acknowledgments: Tony Corleto serves as general counsel for Pop Warner football. He defends concussion litigation. In addition to being an attorney, Alia Najjar is a licensed medical doctor. Before entering the legal profession, she studied at the University of Texas Southwestern Medical School and completed two years of a general surgery residency in Houston, Texas, including neurosurgery, cardiovascular surgery, trauma surgery and pediatric surgery.
©2018 Wilson Elser, LLP. Reprinted by permission.
