Long-Term Consequences of Repetitive Brain Trauma: Chronic Traumatic Encephalopathy

While concussion, as with any form of traumatic brain injury (TBI), needs to be taken seriously,  the impact on an athlete's day-to-day life is usually shortlived.  Three-quarters of concussed high school athletes in one recent study (1) were found to be symptom-free within a week; only 15% had symptoms lasting more than a week but less than a month, and only a very small number (1.5%) were still experiencing symptoms more than a month after injury.

Recent evidence, however, suggests that "mild" TBI, including repetitive concussive and subconcussive brain trauma (2), may lead to long-term or progressive symptoms (postconcussion syndrome), disability, and pathologic changes, especially in cases of repetitive concussion:

• Repeated concussion is associated with neuropsycyhological deficits, electrophysiologic changes, and metabolic abnormalities measured using brain magnetic resonance spectroscopy (MRS).
• Closed head injury, even in a mild form, is a leading cause of both short-term and long-term cognitive impairment of athletes, particularly those in contact sports such as football, boxing, soccer, rugby, lacrosse and hockey.
• While the majority of athletes who experience a concussion can be expected to recover, the danger is increased by a second concussion, or returning to play from a concussion before the brain has fully healed, which recent studies suggest takes much longer than previously thought.

In an unknown percentage of cases, an athlete can suffer a distinct neurodegenerative condition called chronic traumatic encephalopathy (C.T.E.), a progressive disease in which symptoms do not appear until many years after an individual finishes their playing career, and may be the result of repeated concussive or subconcussive blows to the head. While most documented cases of C.T.E. have been reported in former professional athletes (3), C.T.E. has more recently been documented in younger athletes, including an 18-year-old football player (4).

Symptoms  

The symptioms of CTE are insidious:

• Memory loss
• Irritability
• Outbursts of aggressive or violent behavior
• Confusion
• Speech abnormalities (slurred speech),
• Cognitive decline (concentration)
• Gait abnormalities
• Unsteadiness
• Headaches
• Parkinsonism
• Mood disorders (depression)
• Paranoia
• Poor insight/judgment
• Apathy
• Hyperreligiousity
• Visual abnormalities (13)

Stages of C.T.E.

Three stages of the disease have been identified:

Stage 1: Deterioration in attention, concentration, and memory, as well as disorientation and confusion, and occasionally accompanied by dizziness and headaches. 

• Symptom onset: The first symptoms in confirmed cases of C.T.E. were noticed at ages between 25 and 76 years, with a mean of 42.8 years.
• One third were symptomatic at time of retirement from sport;
• Half were symptomatic within 4 years of stopping play.

Stage 2: Social instability, erratic behavior, lack of insight, poor judgment, memory loss and initial symptoms of Parkinson disease

Stage 3: General cognitive disfunction progressing to dementia, often accompanied by full-blown Parkinsonism, as well as speech and gait abnormalities. 

In most reported cases, the disease slowly progressed for several decades, and was irreversible.

At-risk groups

Although historically, CTE has been primarily associated with boxing, CTE may also occur as a consequence of American football, hockey, wrestling, rugby and exposure to blast or concussive injury associated with military service (13).

A 2012 study (13) by researchers at Boston University's Center for the Study of Traumatic Encephalopathy found evidence of CTE in 80% of individuals with a history of repetitive mild traumatic brain injury, findings the authors said "suggests that repetitive mild traumatic brain injury alone is sufficient to trigger CTE in some people." 

Repetitive closed head injury, however, occurs in a wide variety of contact sports including:

• Football
• Boxing
• Wrestling
• Rugby
• Hockey
• Lacrosse
• Soccer
• Skiing

Sub-concussive hits 

Athletes in collision sports such as football may experience over one thousand hits during the course of a single season, precisely the kind of "repeated sublethal brain trauma" a recent study suggests may lead to C.T.E., even if none, individually, leads to a formal diagnosis of concussion.  

In a groundbreaking 2010 study (5) by researchers at Purdue University, athletes repeatedly subjected to such so-called "sub-concussive hits" (particularly offensive and defensive linemen) were shown to have measurable impairment of neurocognitive function (primarily visual working memory) on neurocognitive tests, as well as altered activation in neurophysiologic function on sophisticated brain imaging tests (fMRI), even though they displayed no clinically-observable signs of concussion,  

Moreover, even though the players in the Purdue study who suffered short-term cognitive impairment from repeated sub-concussive blows appeared to fully recover cognitive function before the next season, exhibiting results on fMRI and neurocogntive tests comparable to their previous baseline scores, the Purdue researchers cautioned that return to baseline did not necessarily mean that there was 100% recovery.  Indeed, the findings led Randall Benson, a neurologist at Wayne State University in Detroit, to suggest that the Purdue researchers may have taken what amounted to a "real-time snapshot" of the early stages of CTE, and that it was possible that the damage would only be known over the long term, years later. 

Since publication of the Purdue study, similar findings have been made by researchers at the University of Rochester Medical Center (URMC) (11). In measuring before-and-after data from the brains of a group of nine high school football and hockey players using diffusion tensor imaging (DTI), researchers found subtle evidence of axonal injury at the cellular level among six of athletes who were not diagnosed with concussion but sustained many sub-concussive blows during the normal course of play.

The abnormalities disclosed on post-season DTI scans among the players were closer to the the scan of the one player with diagnosed concussion than to the normal brains in the control group. Axons, which are like cables woven throughout brain tissue, swell up when traumatic brain injury occurs. The imaging changes also strongly correlated with the number of head hits (self-reported by the athletes in a diary), the symptoms experienced, and independent cognitive tests, said lead author Jeffrey Bazarian, M.D., M.P.H., associate professor of Emergency Medicine at URMC. 

A 2013 study by researchers at URMC and the Cleveland Clinic (12) also found evidence of brain damage in college football players from sub-concussive hits in the form of elevated levels of a protein in the blood usually present only in the brain. The presence of the S100B protein triggers the release by the body of antibodies which can then leak back into the brain through the damaged blood-brain barrier, where they are thought to attack brain tissue. The highest protein levels were found among players who sustained the most hits to the head during games and practices.  

Link between sub-concussive blows and CTE 

The severity of CTE seems to correlate with the length of time engaged in the sport and the number of traumatic injuries, although whether a single TBI can trigger the onset of C.T.E., the number of concussions and/or amount of cumulative subconcussive trauma necessary to produce such pathology remain speculative, leading some experts to conclude that, as of yet, "no reasonable basis exists to predict which athletes might be at risk other than perhaps to identify very broadly those involved in sports with exposure to repeated high-impact forces to the head (e.g boxing, American football)."