“Punch-drunk syndrome” and the history of contact sports and brain damage

 

By Tré LaRosa 
NeuLine Health

After a career of making headlines for his football prowess, Tony Dorsett made the news for a heartbreaking reason related to that same professional football tenure: He and two other NFL players were diagnosed as having signs of chronic traumatic encephalopathy. Chronic traumatic encephalopathy, usually shortened to just CTE, is a “progressive neurodegenerative disease that occurs in association with repetitive traumatic brain injury experienced in sport and military service” and is “characterized by the accumulation of phosphorylated tau protein in neurons and astrocytes in a pattern that is unique from other tauopathies, including Alzheimer’s disease.” Often, CTE is misdiagnosed as Alzheimer’s or amyotrophic lateral sclerosis (ALS).

Tony Dorsett was not the first high-profile instance of a professional athlete potentially having CTE. Since CTE is a complicated tauopathy — which are “neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain” — like Alzheimer’s, it can only be diagnosed posthumously through an autopsy and studying certain sections of the brain. From the Mayo Clinic: “a CTE diagnosis requires evidence of degeneration of brain tissue and deposits of tau and other proteins in the brain that can be seen only upon inspection after death.” Tragically, there are three high-profile cases that preceded Mr. Dorsett’s possible CTE diagnosis. These are the cases of Junior Seau, Dave Duerson, and Ray Easterling, all of whom died by suicide and whose brains were found to have the traditional characteristics of CTE. In a separate study, published in 2017 in the Journal of American Medical Association, researchers investigated a sample of 202 deceased football players across different levels of play. For those who played professional football, 110 of 111, or 99%, were neuropathologically diagnosed with CTE. While CTE had been documented for nearly a century at this point, this landmark study forced the community to acknowledge just how widespread this disease may be.

CTE was previously known as dementia pugilistica or “punch-drunk syndrome” for its association with former boxers demonstrating declining ability, memory loss, and lack of coordination. The hallmark risk factor that separates the syndrome from other tauopathies and dementias is repeated trauma to the head, otherwise known as traumatic brain injuries, or TBIs. It’s this repeated trauma where things become an issue for contact sports.

When it comes to contact sports, the term “concussion” is frequently used. But what exactly does this term mean, and how exactly are concussions linked to CTE? Concussions themselves are a form of TBI, though they are typically considered “mild” but it’s in this definition where things get complicated. A page about sports-related head trauma published on the American Association of Neurological Surgeons’ website does a fantastic job explaining the differences between an assortment of brain injuries, but the gist is that concussions are “considered to be diffuse brain injuries that traumatically induce alterations of mental status. A concussion may result from shaking the brain within the skull and, if severe, can cause shearing injuries to nerve fibers and neurons.” Repeated shaking of the brain within the skull, such as due to football players tackling one another hundreds of times a season or boxers getting repeatedly punched in the skull, results in a series of subconcussive blows to the head. Subconcussive impacts are impacts that usually do not result in symptoms and are not severe enough to rise to the diagnosis of concussions.

In the past, it was believed that one needed to experience serious head trauma to be at risk of developing CTE. While it’s clear that experiencing multiple concussions does increase the likelihood one will develop CTE, in one study, it was found that nearly 20% of athletes that were diagnosed with CTE had never had any diagnosed concussions. Dr. Lee Goldstein, who was one of the study coauthors, states “It’s the hits to the head, not concussion, that trigger CTE.” Dr. Ann McKee, another study coauthor, explicitly states to “reduce CTE risk, there must be a reduction in the number of head impacts.” The authors hypothesize that repeated subconcussive impacts cause “blood vessels to leak proteins into adjacent blood tissues, inflaming them” which may explain why hundreds of subconcussive hits, even if never considered “concussions,” can result in dramatic alterations of brain structure and mental function.

As CTE has become more commonly researched and reported on, researchers have become increasingly interested in understanding the different pathophysiology and clinical presentations of Alzheimer’s and CTE. As neither Alzheimer’s or CTE can be definitively diagnosed in living patients and both have extensive ongoing research in understanding the mechanisms of action, determining exact differences is not a feasible endeavor. In terms of the characteristic tau protein, one study that investigated the differences between the tau protein in those who had CTE compared to those who Alzheimer’s, the authors stated “although the observed tau isoforms are common between AD and CTE, the brain lesions involving tau are distinct in both diseases, and each tau progression pattern is different.” Further, the authors conclude with a compelling statement that they noted that there was mixed pathology displaying tau characteristic of CTE and Alzheimer’s in some TBI patients, indicating TBI may be a risk factor for both syndromes. This suggestion, that CTE and Alzheimer’s may have similar but distinct pathologies was reiterated by authors of another study titled “Alzheimer’s disease and chronic traumatic encephalopathy: distinct but possibly overlapping disease entities” where they concluded, “a single individual may possess neuropathological features of both conditions.” Finally, in yet another study, researchers “discovered an unidentified element adjacent to the tau of CTE, which does not exist in the Alzheimer’s tau” thus also showing that these two syndromes do have distinct pathophysiological differences.

The evidence is clear that repeated head trauma, concussive or not, either in contact sports or otherwise, has long-term consequences for brain health. There needs to be more evidence to not only understand the differences of Alzheimer’s and chronic traumatic encephalopathy, but also to more broadly understand their mechanisms of action, the risk factors, and biomarkers. Other considerations include how researchers can monitor head trauma and establish when an athlete may be reaching a point of high likelihood for developing CTE. Fortunately, just this year, clinicians published criteria for diagnosing a clinical disorder called “traumatic encephalopathy syndrome,” which is linked to CTE. This means doctors are nearer than ever to diagnosing CTE in living patients. Ongoing research should also elucidate where EEGs may fit into the mix of diagnosing and treating CTE. Hopefully, with better diagnostic tools, including the criteria for diagnosing CTE in living patients and the use of routine EEGs to understand incremental neurological changes in athletes, we are closer to treating and preventing CTE altogether.

Resources:

     

     

    Brain-Computer Interface and Its Uses

    Brain-Computer Interface and Its Uses

    Ever wanted to control your computer with your mind? In the world of neuroscience, this is already possible.

    A brain-computer interface (BCI) or a brain-machine interface (BMI), is “defined as a system that measures and analyzes brain signals and converts them in real-time into outputs that do not depend on the normal output pathways of peripheral nerves and muscles”.

    read more
    Biomarkers, how they influence the understanding of health conditions, and Alzheimer’s biomarkers

    Biomarkers, how they influence the understanding of health conditions, and Alzheimer’s biomarkers

    Health conditions do not exist in a vacuum. You can’t separate a condition from the broader world of cells, tissues, organs, humans, populations, or external factors. Even conveying the scope of a condition can be a perplexing ordeal. We don’t first recognize conditions without understanding how the affected individual is supposedly abnormal compared to a person who does not appear to be affected by any condition.

    read more
    The History of Epilepsy

    The History of Epilepsy

    Epilepsy has been recorded as long ago as 2000 BC and was believed to be an illness inflicted by the gods, or possession of evil spirits. Hippocrates instead attributed the disease, then called the ‘sacred disease’, to a medicinal cause, and laid the groundwork for the world to see epilepsy as a neurological condition worthy of education and support.

    read more