Summary: Study confirms that repeated head injuries, concussions, and traumatic brain injury are the chief risk factors for the development of CTE.
Source: Boston University
During the past 17 years, there has been a remarkable increase in scientific research concerning chronic traumatic encephalopathy (CTE) with researchers at the BU CTE Center at the forefront.
While some sports organizations like the National Hockey League and World Rugby still claim their sports do not cause CTE, a new review of the evidence by the world’s leading CTE expert strengthens the case that repetitive head impact (RHI) exposure is the chief risk factor for the condition.
CTE became national news in the United States in 2007, but it wasn’t until 2016 that the National Institute of Neurological Disorders and Stroke/National Institute of Biomedical Imaging and Bioengineering (NINDS-NIBIB) criteria for the neuropathological diagnosis of CTE were published, and they were refined in 2021.
Rare, isolated case studies reporting aberrant findings or using non-accepted diagnostic criteria have been disproportionately emphasized to cast doubt on the connection between RHI and CTE.
In a review article in the journal Acta Neuropathologica, Ann McKee, MD, chief of neuropathology at VA Boston Healthcare System and director of the BU CTE Center, stresses that now over 600 CTE cases have been published in the literature from multiple international research groups. And of those over 600 cases, 97 percent have confirmed exposure to RHI, primarily through contact and collision sports.
CTE has been diagnosed in amateur and professional athletes, including athletes from American, Canadian, and Australian football, rugby union, rugby league, soccer, ice hockey, bull-riding, wrestling, mixed-martial arts, and boxing.
What’s more, 82 percent (14 of the 17) of the purported CTE cases that occurred in the absence of RHI, where up-to-date criteria were used, the study authors disclosed that families were never asked what sports the decedent played.
According to the researchers, despite global efforts to find CTE in the absence of contact sport participation or RHI exposure, it appears to be extraordinarily rare, if it exists at all. “In studies of community brain banks, CTE has been seen in 0 to 3 percent of cases, and where the information is available, positive cases were exposed to brain injuries or RHI.
In contrast, CTE is the most common neurodegenerative disease diagnosis in contact and collision sport athletes in brain banks around the world. A strong dose response relationship is perhaps the strongest evidence that RHI is causing CTE in athletes,” she added.
“The review presents the timeline for the development of neuropathological criteria for the diagnosis of CTE which was begun nearly 100 years ago by pathologist Harrison Martland who introduced the term “punch-drunk” to describe a neurological condition in prizefighters,” explained McKee, corresponding author of the study.
The review chronologically describes the multiple studies conducted by independent, international groups investigating different populations that found CTE pathology in individuals with a history of RHI from various sources.”
CTE is characterized by a distinctive molecular structural configuration of p-tau fibrils that is unlike the changes observed with aging, Alzheimer’s disease, or any other diseases caused by tau protein.
Funding: Funding for this research was provided by the National Institute of Neurological Disorders and Stroke (U54NS115266; R01NS119651; U01 NS 086659), National Institute on Aging (P30AG13846; U19AG06875; R01AG062348; RF1AG057902; K01AG070326), Department of Veterans Affairs (101BX002466, 101BX004613, BX004349), the Nick and Lynn Buoniconti Foundation, Andlinger Foundation, National Football League (NFL) and World Wrestling Entertainment (WWE) through unrestricted gifts, the Mac Parkman Foundation, and the National Operating Committee on Safety for Sports Equipment (NOCSEA).
Chronic traumatic encephalopathy (CTE): criteria for neuropathological diagnosis and relationship to repetitive head impacts
Over the last 17 years, there has been a remarkable increase in scientific research concerning chronic traumatic encephalopathy (CTE).
Since the publication of NINDS–NIBIB criteria for the neuropathological diagnosis of CTE in 2016, and diagnostic refinements in 2021, hundreds of contact sport athletes and others have been diagnosed at postmortem examination with CTE. CTE has been reported in amateur and professional athletes, including a bull rider, boxers, wrestlers, and American, Canadian, and Australian rules football, rugby union, rugby league, soccer, and ice hockey players.
The pathology of CTE is unique, characterized by a pathognomonic lesion consisting of a perivascular accumulation of neuronal phosphorylated tau (p-tau) variably alongside astrocytic aggregates at the depths of the cortical sulci, and a distinctive molecular structural configuration of p-tau fibrils that is unlike the changes observed with aging, Alzheimer’s disease, or any other tauopathy.
Computational 3-D and finite element models predict the perivascular and sulcal location of p-tau pathology as these brain regions undergo the greatest mechanical deformation during head impact injury. Presently, CTE can be definitively diagnosed only by postmortem neuropathological examination; the corresponding clinical condition is known as traumatic encephalopathy syndrome (TES).
Over 97% of CTE cases published have been reported in individuals with known exposure to repetitive head impacts (RHI), including concussions and nonconcussive impacts, most often experienced through participation in contact sports.
While some suggest there is uncertainty whether a causal relationship exists between RHI and CTE, the preponderance of the evidence suggests a high likelihood of a causal relationship, a conclusion that is strengthened by the absence of any evidence for plausible alternative hypotheses.
There is a robust dose–response relationship between CTE and years of American football play, a relationship that remains consistent even when rigorously accounting for selection bias. Furthermore, a recent study suggests that selection bias underestimates the observed risk.
Here, we present the advances in the neuropathological diagnosis of CTE culminating with the development of the NINDS–NIBIB criteria, the multiple international studies that have used these criteria to report CTE in hundreds of contact sports players and others, and the evidence for a robust dose–response relationship between RHI and CTE.