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

 

While all concussions, as traumatic brain injuries (TBI), need to be taken seriously, relatively few have long term health effects.  Three quarters of concussed high school athletes in one recent study were found to be symptom-free within a week; only 15% had symptoms lasting more than a week but less than a month, and 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 trauma¹, can lead to devastating long-term or progressive symptoms (postconcussion syndrome), disability, and pathologic changes, especially in cases of repetitive concussion or mild TBI:

• Repeated concussion is associated with neuropsycyhological deficits, electrophysiologic changes, and metabolic abnormalities by brain magnetic resonance spectroscopy (MRS).
• Closed head injury, even in 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 are expected to recover, the danger is greatly increased by a second concussion.

In some cases, an athlete can suffer a distinct neurodegenerative condition called chronic traumatic encephalopathy (CTE), a progressive disease in which symptoms do not appear until many years after an individual experiences repeated concussive or subconcussive blows to the head. While most documented cases of CTE have been reported in former professional athletes,² CTE has now been documented in an 18-year-old football player.³

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

Stages

Three stages 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 CTE 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

Nine out of ten of confirmed cases of CTE occurred in athletes, mostly in professional boxers (85%), football players (11%), but also in one professional wrestler and one soccer player.

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

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

Athletes in collision sports such as football, for instance, may experience thousands of hits during the course of a single season, precisely the kind of "repeated sublethal brain trauma" a recent study says results in CTE, even if none are serious enough to lead to a formal diagnosis of concussion.  Though they displayed no clinically-observable signs of concussion, athletes repeatedly subjected to such so-called "sub-concussive hits", found a groundbreaking 2010 study by researchers at Purdue University, nevertheless showed 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).  

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 ImPACT tests comparable to their previous baseline scores, the Purdue researchers cautioned that their 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. 

The severity of the disorder 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 CTE remains a mattter of speculation.

Just as some athletes sustain concussion and others do not despite experiencing blows to the head of similar magnitude and number, it is important to note that, while repetitive brain trauma appears to be a necessary variable for the development of CTE, it may not be sufficient.  In other words, all neuropathologically confirmed cases of CTE have had a history of brain trauma exposure but not all individuals with exposure to brain trauma develop CTE.⁴

Among the risk factors may be :

• Genetic predisposition: An important risk factor for CTE may be genetic predisposition, with preliminary studies linking the aloliproprotein E (APOE) gene to worse cognitive functioning in boxers and professional football players, and to prolonged recovery after a single traumatic brain injury.⁴
• Non-genetic variables:  The specific nature of the brain trauma exposure necessary for the development of CTE is not yet known. 
  
  • Few severe TBI versus many subconcussive blows: It is unknown if CTE is any more likely to manifest after a few severe traumatic brain injuries (TBIs) versus numerous repetitive subconcussive impacts.
  • Types and location of hits: Further complications arise when comparing impact exposure and type both between and within sports. A 2010 study of college football players reported in the Journal of Athletic Training,⁵ for instance, found that head-impact exposure differed significantly by position, with linemen (both offensive and defensive) and linebackers receiving more impacts per practice and games than other positions, while lineman, linebackers and defensive backs recieved more impacts to the front of the head than the back, while quarterbacks had a higher pecentage of impacts to the back of the head compared with the front.
  • Age: Age at the time of injury may also affect an individual's risk of developing CTE later in life, although the relationship is not understood.  Because the developing brain is more plastic than the mature brain, younger age at the time of mTBI was originally thought to have a beneficial effect on recovery and expected outcome, allowing a younger athlete to better compensate and recover after brain injury. Current literature, however, indicates that this is not the case; that the developing brain may actually be more susceptible and vulnerable to diffuse brain injury, which leads to more pronounced and prolonged cognitive deficits and hyperactivity.^6,7  "Therefore, it is possible that exposure to repetitive brain trauma at an early age may increase the risk of CTE more than exposure later in life, although this has yet to be proven."⁴
  • Gender. May also play a role, as girls and women appear to be at greater risk for concussion, and post-concussion syndrome-related symptoms.
  • Other health-related variables.  Chronic inflammation associated with obesity, hypertension, diabetes, and heart disease may exacebate neurodegeneration.

Because the study of CTE is in its infancy,⁴ with many critical questions remain.

Prevention and treatment

The "easiest way" to decrease the incidence of CTE is to decrease the number of concussions or mild TBIs in athletes:

• limit exposure to trauma through rule changes and enforcement (such as by penalizing intentional hits to the head, as is happening in football and ice hockey);
• limit an athlete's exposure to impacts that may result in concussion or mTBI from subconcussive blows by:
  
  • Reducing the number and length of full-contact practices.  Practice alone is responsible for up to 1500 impacts of 10g or more for some football players.  Ivy League colleges have taken the lead and recently began implementing this policy; anecdotal evidence in one youth football program in Connecticut suggests it reduces the number of concussions;
• limiting the number of hits a player receives over the course of a season, as is being proposed by the Sports Legacy Institute.
• use of more conservative return to play guidelines:
  • the absence of observable symptoms may not be a reliable guidepost (some indications of impaired brain function are not detectible except with very sophisticated equipment)
  • return to play guidelines might require at least 4 to 6 weeks to facilitate more complete recovery and to protect against reinjury, as a second concussion occurs much more frequently in the immediate period after concussion.
  • animal studies suggest there is an expansion of brain injury and functional recovery slowed if the animal is subjected to overactivity within the first week (supporting the concept of "cognitive rest" recommended for children and adolescents);
• proper care and management of mild TBI; and
• player and coach education.

For the most comprehensive, up-to-date concussion information on the Internet, click here. 

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Sources: 

McKee A, Cantu R, et. al. Chronic Traumatic Encephalopathy in Athletes: Progressive Tauopathy After Repetitive Head Injury. J Neuro Exp. Neurol  2009; 68(7): 709-735

Gavett B, Stern R, Cantu R, Nowinski C, McKee A. Mild traumatic brain injury: a risk factor for neurodegeneration.  Alzheimer's Research & Therapy 2010; 2:18

Galetta KM, Barret J, Allen M, et. al. "The King-Devick test as a determinant of head trauma and concussion in boxers and MMA fighters." Neurology 2011; Prepublished online February 2, 2011.

Daneshvar DH, Baugh CM, et. al. Helmets and Mouth Guards: The Role of Personal Equipment in Preventing Sports-Related Concussion.  Clin Sports Med 2011;30:145-163. 

1. Talavage T, Nauman E, Breedlove E, et. al. Functionally-Detected Cognitive Impairment in High School Football Players Without Clinically-Diagnosed Concussion. J Neurotrauma. 2010; DOI: 10.1089/neu.2010.1512.

2.  Schatz P, Moser RS, Covassin T, Karpf.  Early Indicators of Enduring Symptoms in High School Athletes with Multiple Previous Concussions.  Neurosurgery (accepted for publication); 2011 at n. 3-5.

3.  Boston University Center for Alzheimer's Research. Selected CSTE Cases: Eighteen year old high school football player. 2010;  http://www.bu.edu/cste/case-studies/18-year-old/ (Accessed March 2, 2011).

4.  Stern R, Riley D, Daneshvar D, Nowinski C, Cantu R, McKee A. Long-term Consequences of Repetitive Brain Trauma: Chronic Traumatic Encephalopathy.  Phys. Med. & Rehab. 2011;3;S460-S467. DOI:10.1016/j.pmrj.2011.08.008.

5.  Crisco JJ, Fiore R, Beckwith JG, et al. Frequency and location of head impact exposures in individual collegiate football players.  J. Athl Train 2010;45:549-559.

6.  Field M, Collins MW, Lovell MR, Maroon J. Does age play a role in recovery from sports related concussion? A comparison of high school and collegiate athletes.  J Pediatr. 2003;414:546-553.

7.  Pullela R, Raber J, Pfankuch T. et al. Traumatic injury to the immature brain results in progressive neuronal loss, hyperactivity and delayed cognitive impairments.  Dev Neurosci 2006;28:396-409. 

Posted February 17, 2010; revised and updated November 5, 2011; revised and updated March 1, 2012