Concussion: Long Term Sequelae—The Controversy

Concussion: Long Term Sequelae—The Controversy

Rajiv Saigal, MD, PhD

Mitchel Berger, MD

Neither of the following authors nor any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Dr. Berger and Dr. Saigal.


The possibility of long-term neurologic deficits from repetitive head trauma first appeared in medical literature in the 1920s, but it has gained considerable public attention in recent years. First described as “punch-drunk syndrome” in boxers by Martland in 1928,1 chronic traumatic encephalopathy (CTE) is the modern term for this neurodegenerative disorder. Yet this clinical entity that is nearly a century old remains controversial. Although there are increasing neuropathological data from deceased, former athletes, there remains a paucity of systemic or prospective studies to understand who is at risk or why some develop the condition and some do not. Many athletes who sustain repeated head impacts do not go on to develop CTE. Although most recent media attention has focused on CTE, other possible long-term sequelae exist across a spectrum from mild cognitive impairment (MCI) to Alzheimer disease to CTE. What risk factors cause some to develop long-term sequelae and others not? How much risk does repeated head trauma entail? When is it safe for a concussed athlete to return to play (RTP)? These remain important, unanswered questions. This review seeks to answer what is currently known and unknown about the long-term sequelae of repeated mild traumatic brain injury (mTBI) in sports.


Contact sports are highly popular, and approximately 300,000 to 3.8 million sports-related concussions occur annually in the United States.2,3,4,5 In the subset of American high school athletes, approximately 63,000 sports-related concussions occur annually and require removal from play; 63% of these are in football.6 Female athletes have higher concussion rates than male athletes in common sports: 0.85 concussions per 1000 games in female versus 0.45 per 1000 in male basketball players and 1.8 per 1000 in female versus 1.38 per 1000 in male soccer players.7

Concussion is closed mTBI with posttraumatic amnesia or confusion.8 Common clinical symptoms in the postconcussive syndrome include impaired attention and concentration, headache, impaired memory, cognitive dysfunction, nausea, vomiting, mood changes, irritability, light and sound sensitivity, sleep disturbance, and fatigue.8 Concussion and mTBI are most often used interchangeably, although some groups define subtle distinctions between the two.9 The Fourth International Conference on Concussion in Sport defined concussion broadly as a “complex pathophysiological process affecting the brain, induced by biomechanical forces.”9 Rapid symptom onset, loss of consciousness (LOC), direct impact to the head, and relatively quick recovery (often <10 days) may occur but are not required to meet the formal definition.9 Postconcussive symptoms affect up to 50% of patients 1 year after injury.10

The exact force and acceleration required to cause a concussion remains a topic of study. Accelerometers placed in football helmets have yielded quantitative information regarding forces and acceleration required for concussion. Table 28-1 shows these values. National Football League (NFL) studies showed concussive impacts average 98 times gravitational acceleration (98 × 9.8 m/sec2, or 98 g), and nonconcussive impacts average 60 g.11 Additional study is needed to gather similar information from other levels of competition and other sports.


Several controversial subtopics are related to potential long-term sequelae from repetitive head trauma in sports.
These include subconcussion, MCI, CTE, apolipoprotein E4 (ApoE4), dementia, and RTP guidelines. Each is discussed separately in this chapter.

TABLE 28-1 Impact characteristics predictive of concussion in football

Rotational acceleration 5582.3 rad/sec2
Linear acceleration 96.1 g
Location Top, front, and back of helmet
Data from Bailes JE, Petraglia AL, Omalu BI, Nauman E, Talavage T: Role of subconcussion in repetitive mild traumatic brain injury. J Neurosurg 2013;119(5):1235–1245 and Broglio SP, Schnebel B, Sosnoff JJ, Shin S, Fend X, He X, Zimmerman J: Biomechanical properties of concussions in high school football. Med Sci Sports Exerc 2010;42(11):2064–2071.


Subconcussion is a milder form of TBI not meeting the formal diagnostic criteria for concussion. The characteristic concussion symptoms of headache, visual disturbance, amnesia, confusion, gait or postural instability, and dizziness do not occur in subconcussion.12 Regardless, there is now some evidence that subconcussive blows may also lead to long-term sequelae.13,14,15

Boxers were the first group of athletes noted to have potential long-term neurodegeneration from repeated head trauma, and research has continued to corroborate this early finding. The degree to which this risk is due to concussive or subconcussive trauma is unknown. In one report, neuropsychological (NP) tests, CT, and electroencephalography (EEG)-based evidence showed more bouts correlated with higher cognitive impairment even in young fighters.16 The authors speculated that this could be due to repeated subconcussion.16 In the absence of quantitative data on subconcussions and concussions sustained during training and competition, there are insufficient data to support this claim.

Helmet accelerometer data showed that football players experience between 100 head impacts per season in youth and 1000 in college.12 Even in the absence of concussion, these impacts can cause lasting sequelae. Nonconcussed college athletes scored lower in NP tests and memory than control participants.12,17 Even at the high school level, there is a subset of football players who have no history of diagnosed concussion yet demonstrate altered activation of the prefrontal cortex and impaired visual memory on neurocognitive testing.18 This same group of athletes had higher numbers of accelerometer-recorded impacts to the front and top of the head.18 Follow-up studies using magnetic resonance spectroscopy showed metabolic abnormalities in high school football players after subconcussive trauma.19 Short-term abnormalities in connectivity were seen on functional MRI (fMRI).20 If validated through further study, this presents an opportunity for rules changes to improve player safety, such as decreasing the number of full contact practices in order to decrease the total number of head impacts.

Mild Cognitive Impairment

Mild cognitive impairment is a memory deficit beyond age-related norms, corroborated by either neurocognitive testing or family but with insufficient symptoms to meet diagnostic criteria for dementia; impairment is mild enough that the patient can still complete activities of daily living.21 A 2005 survey-based study assessed whether MCI was associated with repeated concussion in retired professional football players.22 A total of 24% sustained at least three concussions during their professional careers, and this group had a fivefold increased prevalence of MCI.22 Only 17.6% of players with history of concussion believed that it had an enduring effect on cognition. For a survey-based study, there was a relatively high participation rate of 69% (2552 of 3683) in the concussion questionnaire. However, less than 30% (758 of 2552) of the entire cohort completed the MCI-based questionnaire, limiting the interpretation of these data.22

Amateur athletes are also subject to risks of repeated mild TBI. High school athletes with at least three prior concussions showed increased concussion severity, including anterograde amnesia, confusion, and LOC, compared with those without concussion.23 These data support the argument that RTP should be disallowed after three concussions in a season.8,24 According to data recorded from helmet accelerometers in high school football players, there does not appear to be a correlation between number of prior hits to the head and impact threshold for a new concussion.25 In other words, the same magnitude of head impact is required to cause a concussion, whether or not the player has sustained prior concussions. In a comparison of amateur boxers with matched soccer and track athletes, boxers had inferior finger-tapping scores and slight EEG abnormalities but no other difference in neurologic examination findings.26

Chronic Traumatic Encephalopathy

Chronic traumatic encephalopathy is a progressive neurodegenerative disorder caused by perivascular
tau-positive neurofibrillary tangles, with an absence of the amyloid beta deposits seen in Alzheimer disease.27,28 Gross brain disturbances may include atrophy of frontal and temporal lobes, cavum septum pellucidum, ventriculomegaly, corpus callosum thinning, and white matter loss.27 Clinically, patients with CTE may exhibit components of cognition, mood, behavior, and motor dysfunction.27 Case reports from the Center for the Study of Traumatic Encephalopathy (CSTE) at Boston University have shown evidence of CTE pathology in a subset of retired athletes.5,14,28,29,30,31,32,33,34,35,36,37 These former athletes with CTE had a mean exposure to repetitive head trauma of 15.4 years with symptom onset 14.5 years after initial exposure.27 A total of 92% (33 or 36) of cases displayed clinical symptoms before death.30 Table 28-2 shows clinical findings in one case series on CTE.30 Nonetheless, data on CTE correlation to repetitive concussion remain mixed and controversial. Although 84% of diagnosed cases had history of concussion, the remaining ones did not, raising the possibility that subconcussive trauma or other factors may also cause risk.27

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Oct 16, 2018 | Posted by in MUSCULOSKELETAL MEDICINE | Comments Off on Concussion: Long Term Sequelae—The Controversy
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