What is a concussion?

What is a concussion?

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When I was a kid and someone got a concussion, I seem to remember people telling me that it was when your brain impacts the side of your skull, accelerating fast enough to do so despite the cerebrospinal fluid buffer.

But wikipedia doesn't mention this explicitly. Is this just one possible cause for concussions? Is it possible to generalize about them? How much don't we know?

Concussion generally refers to the set of clinical symptoms that are secondary to the head injury and are characteristic by altered state of consciousness like instant onset of transient neurologic dysfunction, lack of consciousness or temporary respiratory arrest and loss of reflexes.

Since it's connected to the head trauma by definition, there is in principium no other cause of it.

The patophysiologic mechanism of concussion is not well understood yet, it's thought it results from two main sources:

  • the acceleration of brain causes increase of pressure
  • the impact of brain on the hard shell causes deformation and sheer stress in brain tissue (probably stronger cause of cytologic changes discussed later on)

These two mechanisms might lead to changes in the tissue structure and also trigger cytologic changes in the astrocytes and neurons such as:

Astrocytes respond to a focal mechanical stimulation by propagating intercellular waves through their network. Mechanically stimulated astrocyte networks show changes in the cytoskeleton, organelle function, and biochemical cascades over time.

The changes in neurons detected in vitro include microstructural changes, direct membrane permeability change and change in the receptor abundance, structure of subunits and

Early evidence showed that these physical insults can affect the properties of important synaptic glutamate receptors that can regulate neurotransmission and plasticity in networks. Moreover, inhibitory synaptic receptor functions can be altered with a physical force, showing that the balance of excitation/inhibition coupling is important to consider when assessing the effects of these physical forces. Perhaps equally important is the alteration in the receptor composition and intracellular signaling that occurs after a microinjury.

Microinjury is also linked to triggering of cell death pathways in brain cells.

The importance of these mechanisms are not yet clearly understood though and there probably are many more playing their role.


  1. Overview study
  2. Robbins and Cotran pathologic basis of disease

The CDC has a nice webpage about concussions and traumatic brain injury, as does the Mayo Clinic. The brain and head move rapidly back and forth due to impact or sudden acceleration or deceleration, in spite of the cerebral spinal fluid bathing the brain cavity. This causes chemical changes in the brain and/or damage to brain cells, affecting brain function.

Symptoms are not always instantaneous; sometimes it can take hours or days for symptoms to arise. There are multiple diagnostic tools that exist, including graded symptom checklists, the Standardized Assessment of Concussion, neuropsychological assessments, and the Balance Error Scoring System. These are summarized in this American Academy of Neurology (AAN) article from 2013.

A Bang to the Brain

Your brain is your body’s command center. Its soft, sensitive tissues float in a cushioning fluid within the hard and sturdy skull. But a swift blow to the head or violent shaking can override these protections and lead to a mild type of brain injury known as a concussion.

More than 1 million mild traumatic brain injuries occur nationwide each year. These injuries can be caused by falls, car crashes or recreational activities like bike riding, skateboarding, skiing or even playing at the playground. More than half of concussions occur in children—often when playing organized sports such as football and soccer.

“Although concussions are considered to be a mild brain injury, they need to be taken seriously. They should not be treated as minor injuries that quickly resolve,” says Dr. Beth Ansel, an expert on rehabilitation research at NIH. With proper care, most people recover fully from a concussion. “But in some cases, a concussion can have a lasting effect on thinking, attention, learning and memory,” Ansel adds.

A single concussion is also known to raise your risk for having another concussion—and a second concussion may be more severe. It’s important to learn to recognize the causes and symptoms of concussion so you can take steps to prevent or treat these head injuries.

“The skull is designed to prevent most traumas to the brain, but it doesn’t really prevent the brain from moving around inside the skull,” says Dr. Frederick Rivara, a specialist in pediatric injuries and prevention at the University of Washington in Seattle. “A concussion can arise from the brain moving either rapidly back and forth or banging against the side of the skull.” This sudden movement can stretch and damage brain tissue and trigger a chain of harmful changes within the brain that interfere with normal brain activities.

More serious brain injuries that involve skull fracture, bleeding in the brain or swelling of the brain can be detected with X-rays or other imaging methods. But concussions can be more difficult to identify.

“A concussion isn’t visible from the outside, and you can’t see it with standard imaging tools like MRI and CAT scans,” says Dr. Christopher Giza, a pediatric brain specialist at the University of California, Los Angeles. “Instead we look for the signs and symptoms of abnormal brain function to make a diagnosis.”

Common symptoms include nausea, headache, confusion, dizziness and memory problems. Loss of consciousness occurs in about 1 in 10 concussions. A person with a concussion might have trouble answering basic questions and move in an awkward, clumsy way.

“Symptoms can arise quickly, or they can be delayed and appear over the next day or two,” Rivara adds.

For about 9 in 10 people with concussions, symptoms disappear within 7 to 10 days. Scientists have been working to learn more about those who take longer to recover. In one NIH-funded study, Dr. Keith Yeates of Ohio State University looked at 8- to 15-year-olds treated in an emergency room for mild traumatic brain injury.

“We found that the majority of these kids recovered quite quickly or showed no increase in symptoms at all,” Yeates says. “But a subgroup of kids, about 10% or 20%, showed a dramatic onset of symptoms after their injury and persistent symptoms that in some cases remained even 12 months after the injury.”

Body-related symptoms, such as headache and dizziness, tended to fade fairly quickly, the researchers found. But thinking-related symptoms, including problems with memory and paying attention, tended to linger in some kids throughout the year-long study. Children who had lost consciousness or had some additional abnormality that showed up on MRI scans after the injury had an increased risk for lasting problems.

“These kids were also more likely to have what looked like significant reductions in overall quality of life. And there was some evidence they were more likely to have academic problems than the kids without persistent symptoms,” Yeates says.

Yeates and others continue to explore ways to predict a person’s response to concussion. Much remains unknown about the underlying biology and outcomes of mild head injuries. Some NIH-funded researchers are looking at how injury and recovery processes differ in immature and adult brains. Other scientists are examining the problems that can arise from repeated injuries to the brain.

Researchers know that immediately after a concussion, the brain is especially vulnerable to having a second, more serious injury. But it’s not clear why—or how long that vulnerable period lasts. Giza and his colleagues have found that a single mild injury reduces the brain’s use of the sugar glucose as a fuel, at least in rats. A second mild injury 24 hours later leads to an even steeper drop in glucose use and memory problems that last longer. But when the brain has several days to recover, and the use of glucose returns to normal, a second mild brain injury seems to be no worse than the first.

“The finding suggests that when you superimpose 2 injuries on top of each other, the consequences can be greater,” Giza says. The brain’s use of glucose might be a way to assess risk and recovery time. “But we don’t yet have a clear understanding of what happens in the human brain after first and second injuries,” Giza adds.

Studies have found that the risk for a second injury is greatest in the 10 days following an initial concussion. If you suspect that someone has a concussion, make sure they stop whatever activity they’re doing, especially if they’re involved in a sport. Their brain dysfunction might not only cloud their thinking. It can also slow reaction times and affect their balance so they become more likely to have another injury.

“If someone has symptoms of concussion, they shouldn’t try to finish the quarter or finish the game. They need to be taken out of play right away and be seen by a health care provider,” Rivara says. “The current recommendations are to avoid physical activity for a period of time until all the symptoms have resolved, and then have a gradual return to play.”

Take steps to avoid concussions. “Wear helmets when appropriate, such as if you’re bicycling, skate-boarding or riding a horse,” says Rivara. Athletes can decrease their risk of concussion by wearing proper headgear and following the rules of good sportsmanship. Make living areas safer for seniors by removing tripping hazards such as throw rugs and clutter in walkways, and install handrails on both sides of stairways.

“The bottom line is that we still need to determine the best ways to prevent, accurately diagnose, treat and assess outcomes after mild traumatic brain injury,” says Ansel.

While this research continues, do what you can to prevent concussions. Learn to recognize the symptoms. And make sure that people with signs of concussion stop their activities and seek medical attention.

Blood-brain barrier damage occurs even with mild head trauma

In a new study of adolescent and adult athletes, researchers at Ben-Gurion University of the Negev, Stanford University and Trinity College in Dublin have found evidence of damage to the brain's protective barrier, without a reported concussion.

For the first time, the researchers were able to detect damage to the blood-brain barrier (BBB), which protects the brain from pathogens and toxins, caused by mild traumatic brain injury (mTBI). The results were published this month in the Journal of Neurotrauma.

The researchers studied high-risk populations, specifically professional mixed martial arts (MMA) fighters and adolescent rugby players, to investigate whether the integrity of the blood-brain barrier (BBB) is altered and to develop a technique to better diagnose mild brain trauma.

"While the diagnosis of moderate and severe TBI is visible through magnetic resonance imaging [MRI] and computer-aided tomography scanning [CT], it is far more challenging to diagnose and treat mild traumatic brain injury, especially a concussion which doesn't show up on a normal CT," explains Prof. Alon Friedman, M.D., Ph.D. Dr. Friedman is a groundbreaking neuroscientist and surgeon, who established the Inter-Faculty Brain Sciences School at BGU.

The study shows that mild impact in professional MMA and adolescent rugby can still lead to a leaky BBB. If in a larger study the results are similar, the brain imaging techniques being developed could be used to monitor athletes to better determine safer guidelines for "return to play."

In this study, MMA fighters were examined pre-fight for a baseline and again within 120 hours following competitive fight. The rugby players were examined pre-season and again post-season or post-match in a subset of cases. Both groups were evaluated using advanced MRI protocol developed at BGU, analysis of BBB biomarkers in the blood and a mouthguard developed at Stanford with sensors that track speed, acceleration and force at nearly 10,000 measurements per second.

Ten out of 19 adolescent rugby players showed signs of a leaky blood-brain barrier by the end of the season. Eight rugby players were scanned post-match and two had barrier disruptions. The injuries detected were lower than the current threshold for mild head trauma. The researchers were also able to correlate the level of blood-brain barrier damage seen on an MRI with measurements from the mouthguard sensors.

"The current theory today is that it is the outer surface of the brain that is damaged in a concussion since, during an impact, the brain ricochets off of skull surfaces like Jell-O," Dr. Friedman says. "However, we can see now that the trauma's effects are evident much deeper in the brain and that the current model of concussion is too simplistic."

In the next phase of research, the group plans to conduct a similar study in a larger cohort to determine whether BBB disruptions heal on their own and how long that takes.

"It is likely that kids are experiencing these injuries during the season but aren't aware of them or are asymptomatic," Dr. Friedman says. "We hope our research using MRI and other biomarkers can help better detect a significant brain injury that may occur after what seems to be a 'mild TBI' among amateur and professional athletes."

Concussion Symptoms

Concussions can be tricky to diagnose. Though you may have a visible cut or bruise on your head, you can't see a concussion. Signs may not appear for days or weeks after the injury. Some symptoms last for just seconds others may linger.

Concussions are fairly common. Some estimates say a mild brain trauma is sustained every 21 seconds in the U.S. But it's important to recognize the signs of a concussion so you can take the proper steps to treat the injury.

There are some common physical, mental, and emotional symptoms a person may display following a concussion. Signs of traumatic brain injury include:

  • Confusion or feeling dazed
  • Clumsiness
  • Slurred speech
  • Nausea or vomiting
  • Headache
  • Balance problems or dizziness
  • Blurred vision
  • Sensitivity to light
  • Sensitivity to noise
  • Sluggishness
  • Ringing in ears
  • Irritability or other behavior or personality changes
  • Difficulty concentrating
  • Loss of memory
  • Fatigue or sleepiness
  • Loss of consciousness
  • Forgetfulness such as repeating yourself
  • Slowed response to questions
  • Problems with sleep
  • Depression
  • Problems with taste or smell

Long-Term Symptoms of a Closed Head Injury

The long-term symptoms of a closed head injury vary greatly from person to person, and are dependent upon a number of factors, including:

  • Overall health: People in poor health are more vulnerable to serious head injuries. A head injury can also be more dangerous if you have a previous history of head injuries or an active infection.
  • Prompt medical treatment: The prognosis is best if you receive prompt medical treatment at a facility skilled at treating head injuries.
  • Ongoing physical therapy and rehabilitation: You may need a range of treatments, and consistently engaging in these treatments is your best option for a rapid recovery.
  • The severity of the injury, as well as its location.

Because the brain is your body's command center, virtually every bodily function can be affected by a closed head injury. Emotional, psychological, and behavioral changes are common, as are alterations in cognition and intelligence. Some people suffer anger issues or impulse control problems after experiencing a cosed head injury. Others struggle with fine motor skills, memory, personal relationships, and basic functions such as reading and writing.

Many closed head injury survivors who receive prompt medical treatment will suffer no lasting damage. If, however, you have recently suffered a closed head injury and experience new or worsening symptoms, contact your physician immediately.

How Concussions Work

In the waning years of American vaudeville, a comedy act -- later to be known as "The Three Stooges" -- entered the public's eye. Their slapstick routines regularly consisted of situations often leading to one or more of them being hit, jarred or rattled in the head, and their work was wildly popular.

While admittedly amusing in some fictional contexts, a concussion -- derived from the Latin word concutere, meaning "to shake violently" -- is never a laughing matter in real life. Imagine someone driving without a seatbelt into a concrete wall. When the vehicle suddenly stops, the driver keeps going, and that's what happens to the brain during a concussion. To put it simply: A concussion occurs when the skull stops and the brain keeps moving, resulting in a collision. In an ironic twist, the one bone structure specifically designed to shield our grey matter from injury ends up doing most of the damage [Source: Lew].

Nearly all cases of head trauma fall under the umbrella of what we call "mild traumatic brain injury" (MTBI), an expression that can be used interchangeably with "concussion." Concussions are among the lesser-understood injuries today, and their treatment still continues to evolve. Medical practitioners frequently disagree on how to diagnose and manage concussions of varying grades, or levels of severity. However, some aspects of these injuries aren't up for debate. Evidence has shown that their effects can be permanently debilitative in severe cases [Source: Lew].

Worst-case concussions can even result in death. And while there's a tendency to only associate these injuries with athletics, most cases in the United States are entirely unrelated to sports. So, it's important to understand concussions to facilitate preparedness in the event that you or someone close to you has one. Some of the details provided in this article cover the common causes, symptoms, treatment and prevention methods for mitigating their effects.

Keep reading to learn about some of the immediate and long-term concussion symptoms.

Colored glasses may provide light sensitivity relief post-concussion

Following a concussion or mild traumatic brain injury (TBI), patients may suffer from light sensitivity or photophobia, making it challenging to return to normal activities. The sensitivity may also trigger or exacerbate headaches.

While sunglasses can provide some relief from photophobia, wearing them all the time is not always a practical solution, nor is it pleasant for patients to live in a dark room for days at a time. A new study from the University of Cincinnati (UC), published online this week in the Journal of Athletic Training, assessed the use of colored lenses in post-concussion patients and found wearing certain color-tinted sunglasses may be a good alternative to dark sunglasses.

"While sunglasses can provide some relief, they are not very practical indoors or in low light environments," says Joe Clark, PhD, professor in the Department of Neurology and Rehabilitation Medicine at the UC College of Medicine and lead author of the study. "What is needed is a light mitigation strategy that can be readily employed indoors, which can optimize relief in those who suffer from photophobia, or light sensitivity."

Clark and researchers at the College of Medicine assessed visual symptoms of 51 concussion patients and used frames with varying colored lenses to find out if certain hues provided relief from photophobia.

"We found that 85 percent of patients reporting photophobia had relief of the symptoms with one or more colors -- blue, green, red and purple -- with no reported adverse events," Clark says.

"Sensitivity to light can be common and impact activities of daily life suggesting that light mitigation might improve quality of life in many of these patients. Photophobia is a common symptom for patients following traumatic brain injury. Our goal in this study was to provide medical staff like athletic trainers with a method and means to assess and subsequently provide relief to an athlete who may be experiencing symptoms of photophobia," Clark adds.

The goal is to help the concussion patient feel better as the brain heals. "We compare the colored glasses to being like a brace or cast but for the brain," he says. "It is temporary but prevents further injury or pain."

At least 3.8 million people in the United States sustain a concussion or traumatic brain injury every year, many not for the first time. As with many other health conditions, the presentation of concussion symptoms can vary greatly -- while some individuals exhibit very little to no change in functionality and may report no symptoms at all, others may report confusion, headache, decreased balance and vision disturbances including blurry vision, trouble focusing and sensitivity to light.

Photophobia is so common that many neurosurgical intensive care units consider it standard operating procedure to keep lights dimmed in rooms containing TBI patients says Clark.

In addition to trying colored-lens sunglasses, the article suggests other ways to mitigate photophobia including wearing a wide-brimmed hat when outdoors, adjusting digital screen and device settings to an appropriate hue and brightness or purchasing filters for screens. However, the researchers noted, they do not recommend wearing colored glasses while driving. Certain colors make seeing stop lights or emergency vehicle lights difficult.

"We believe that an athletic trainer, in consultation with team physicians, may find it useful to apply this photophobia assessment and recommend colored glasses to his or her athlete," Clark says. "The use of the colored glasses in the high school, college or other setting can allow a person to engage in some medically approved activities, while minimizing the risk of symptom exacerbation. We believe the use of the colored glasses that provide photophobia mitigation has added benefits superior to dark sunglasses, especially for indoor lighting."

Additional researchers on the study include Jon Divine, MD, a professor in the Department of Orthopaedic Surgery at the UC College of Medicine and head team physician for University of Cincinnati Athletics.

Sequelae of mTBI

Post Concussive Symptoms and Cognitive Deficits

Common post-concussive symptoms include headache, dizziness, fatigue, sleep disturbances, memory problems, balance problems, sensitivity to sound or tinnitus, concentration difficulties, and irritability. These symptoms are notably non-specific and are associated with many other diseases. Nonetheless, several studies have reported higher rates of these symptoms in patients after mTBI than in patients with no injury or extra-cranial trauma without TBI 64 , 99 - 100 . The percentage of patients who suffer from persistent post-concussive symptoms diminishes with time after injury. Less than 25% of patients are likely to have problems lasting more than 12 months after injury 11 . Although cognitive complaints are fairly common after mTBI, measurable cognitive deficits are generally only present after severe or moderate TBI 101 - 102 . There is little evidence of objective cognitive deficits after mTBI 103 .

Motor, Balance, and Cranial Nerve Abnormalities

In general, objective findings after mTBI are absent. Balance problems are emerging as a promising exception to this rule. In one study of 37 mTBI patients, testing of saccades, oculomotor smooth pursuit, upper-limb visuomotor function and neuropsychologic domains was performed and the results compared to uninjured control patients. At one year after injury, eye and upper limb movement, but not cognitive function remained impaired in the mTBI patients 104 . In a more recent study, the same group found that eye movement impairment was significantly worse in mTBI patients suffering from post-concussive syndrome relative to mTBI patients with good recovery 105 .

Psychiatric Diagnoses

Many studies have found an association between TBI of all severities and major depressive disorder 63 , 106 - 107 . This observed association was not likely to be explained by depression prior to injury however prior mood disorder may be an increased risk for TBI 108 - 109 . While there are few studies of relationship between mania or bipolar disorder and TBI, the existing evidence suggests that there is not a strong relationship between them 110 - 112 . There is limited evidence supporting an association between mTBI and PTSD in military populations. In a study of 2,525 soldiers returning after a one year deployment to Iraq, researchers identified a clear association between PTSD and mild TBI with LOC (OR, 2.98 95% CI, 1.70𠄵.24) 64 . A second cross-sectional study of 2,235 Afghanistan and Iraq war veterans also found an association between PTSD and mTBI 113 . However, two studies of civilian populations found no relationship between mTBI and PTSD 114 - 115 .

Second Impact Syndrome

Second impact syndrome (SIS) is a dreaded, rare complication of mTBI that occurs after a patient suffers a second mTBI while remaining symptomatic from the first. Typically, a patient will suffer a head injury during play resulting in post-concussive symptoms. After returning to play while still suffering symptoms they sustain a second, apparently minor head trauma, and rapidly suffer depressed mental status resulting in death or a persistent vegetative state. It is postulated that this disorder is caused by disordered cerebral autoregulation resulting from the initial TBI. The condition has mainly been reported in young men who play contact sports. The term SIS was first coined by Saunders and Harbaugh 116 , however a similar syndrome was previously described by Schneider 117 .

While SIS has become firmly fixed in the minds of clinicians as an important complication of mTBI, there is some question regarding whether it is a true clinical entity 118 . A critical review of reported cases of SIS found that most did not meet a reasonable clinical definition of SIS. Cases often lacked a neuropathologic evidence of unexplained cerebral swelling 119 . Even more problematic, most of the reported cases of precipitous neurologic collapse after a seemingly minor trauma occurred in the absence of any documented 𠇏irst impact”. Of the seventeen cases reviewed, only five where classified as “probable SIS”. Given this analysis it is reasonable to conclude that the term SIS is inaccurate. Diffuse cerebral swelling can very rarely occur after mTBI, principally in children and adolescents, however a second mTBI is not required.


While there is sufficient evidence to support a causal relationship between moderate or severe TBI and the development of unprovoked seizures, the evidence is limited for an association between seizures and mTBI 24 . In non-military TBI populations, there is a 3.6 fold increase in the incidence of seizures relative to non-injured patients after TBI of all severities. After severe TBI, there was a 17 fold increase in seizure incidence which declined to 2.9 fold in moderate TBI patients. For mTBI patients with loss of consciousness or post traumatic amnesia, the incidence of seizures was 1.5 times that of controls (95% CI 1.0 – 2.2) 94 , 120 . These studies were limited in that pediatric patients, who have a higher baseline incidence of seizures than adults, were not analyzed separately from adults. Post-traumatic seizure risk is greatest in the first year after injury. After 4 years, TBI patients are no longer at increased risk relative to uninjured subjects 121 .

Dementia and Neurodegeneration

Alzheimer's disease is the most common neurodegenerative disease and results in progressive dementia and eventual death. Familial or early onset Alzheimer's disease is caused by specific mutations and comprises approximately 10% cases. The remaining 90% of cases are referred to as sporadic. Although the mechanisms of disease progression in sporadic Alzheimer's disease are not known, it likely results from a combination of genetic and environmental factors. TBI is the strongest known environmental exposure associated with subsequent development of sporadic Alzheimer's disease. A retrospective cohort study of World War II veterans with documented closed head injury demonstrated an increase risk of Alzheimer's type dementia relative to non-head injured controls (Hazard ratio 2.00, 95% CI 1.03-3.90) 122 . A meta-analysis of seven case control studies revealed similar results 123 .

Dementia pugilistica, also known as chronic traumatic encephalopathy, is a neurodegenerative condition that affects athletes in sports that involve repeated head trauma such as boxing and mixed martial arts 124 . Characteristic neuropathologic changes include cerebellar damage, cortical damage, and other scarring of the brain substantia nigral degeneration neurofibrillary tangles in the cerebral cortex and temporal horn areas and abnormalities of the septum pellucidum. Autopsy of professional football players who died in their forties after developing dementia also showed neurodegenerative changes consistent with chronic traumatic encephalopathy 125 - 127 . Neuropsychologic deficits associated with dementia pugilistica have been found in some studies 128 - 129 but not others 130 - 131 .

Parkinsonism is a constellation of symptoms including tremor, rigidity, and bradikinesia, and postural instability and is caused by loss of central dopamine. Very little has been reported regarding association between TBI and parkinsonism, however, several case-control studies have shown an increased risk after mTBI with LOC or post-traumatic amnesia 132 - 133 . The risk for the development of parkinsonism appears to increase with severity of TBI 132 , 134 .


Recently, concern about the long-term effects of head trauma related to contact sports has skyrocketed. At the center of the controversy are the rising number of former football players suffering from a neurodegenerative condition and the National Football League (NFL), which has largely denied any link between football and degenerative disease.

Numerous stories have been written about the tragic deaths of former athletes, and Will Smith starred in a film about the forensic pathologist who first identified abnormalities in a former NFL player’s brain.

As media attention increases, the underlying biology is rarely the focus. Reporting is rarely neutral — any head injury is either a sure path to lifelong distress or there is no reason to believe any link at all exists. The reality, however, is murkier.

It is critical to assess what current research reveals, what still needs to be done, and why it is so difficult to make definitive claims.

The question is whether repeated head trauma causing minor brain injuries, such as concussions, can have effects later in life, particularly in the development of the neurodegenerative disease Chronic Traumatic Encephalopathy (CTE). Neurodegeneration associated with repeated head trauma had been described since the 1920s in boxers, but it was not until 2005 that the first case of CTE was diagnosed in an athlete from another sport.

CTE is a debilitating illness. Patients suffer from progressively worsening cognitive, emotional, and physical symptoms, including erratic moods, personality changes, and memory loss. However, these symptoms typically emerge about a decade after initial brain trauma, which makes it difficult to link earlier injury with an eventual CTE diagnosis.

The only way to diagnose CTE is to examine brain tissue after death. Much like Alzheimer’s Disease, CTE causes abnormal buildups of a protein called tau. It is not known how these tau buildups are linked to the behavioral symptoms of CTE, but they are a key marker for diagnosis. Because postmortem analysis is the only way to diagnose CTE, several brain banks dedicated to CTE have been established.

At Boston University, one of the largest CTE brain banks, researchers have examined 165 total brains of former football players and found evidence of CTE in 97% of professional players and 79% of all players.

CTE has also been identified in athletes from other sports, including professional ice hockey and baseball. In a study from the Mayo Clinic, no evidence of CTE was found in 198 people with no history of playing contact sports or other head injuries.

Since CTE seems to occur overwhelmingly in people with a history of repeated minor head trauma, researchers have turned to initial head injuries to understand how CTE develops.

However, linking head trauma to CTE has proved scientifically difficult. Scientists currently think a concussion after a blow to the head causes minor traumatic brain injury, which induces changes in the brain leading to CTE. However, this link is difficult to investigate because concussive impacts and symptoms are heterogeneous, there are no clear diagnostic criteria for concussions, and we have a rudimentary understanding of the changes in the brain following a concussion.

Concussions are caused by forces applied to the brain due to sudden movements of the head. The brain is floating inside the skull in a bath of fluid that provides a buffer between the brain and skull. When sudden impact occurs and the head rapidly stops moving, the brain can continue to move, like when a person is thrown off a bicycle after a sudden stop. The brain can hit the inside of the skull, causing trauma.

There is not a known “impact threshold” where force to the head goes from benign to harmful. While it is possible to put sensors on helmets to detect the exact force exerted on the head during gameplay, this data has not yielded a clear threshold that could be used for diagnosis likely because other factors, including the angle of impact and individual susceptibility, affect concussive risk.

Not only is the threshold for an injury-causing impact unclear, the experiences of people with concussions are diverse. Symptoms include headaches, dizziness, fatigue, and memory impairment.

Contrary to popular belief, loss of consciousness is not required for a concussion. The variability of symptoms makes concussion diagnosis difficult, especially at the time of injury.

Standard sideline concussion tests assess coordination (walking in a straight line), memory (repeating a list of words), and other cognitive skills. However, these standard tests often perform poorly in one study, a standard sideline test detected a concussion in only two of 12 athletes who were later diagnosed. Without a clear picture of causes or symptoms of concussions, identifying, treating, preventing, and researching concussions is difficult.

To understand how concussions lead to CTE, we must first understand the biology of concussions. The period immediately following initial injury is the best understood scientifically.

During normal function, the brain is precisely balanced. Immediately after concussion, the brain is hugely disrupted: there are large shifts in the normal ion balance and non-selective release of neurotransmitters, chemicals that neurons use to communicate with each other, causing a huge surge in random activity.

Following this massive disruption, neurons attempt to re-establish the proper balance in the environment. However, this rebalancing is extremely energetically demanding and often requires more resources than are available, particularly because blood flow providing nutrients and oxygen is also decreased after concussion. It can take weeks for the brain to recover, and during this time, the brain remains in a state of heightened vulnerability to further injury.

While there is some understanding of the chaos that a head injury immediately causes in the brain, scientists do not understand why symptoms persist in some patients much longer than in others or how these changes may cause CTE later in life.

There is a strong correlation between the amount of time someone is exposed to repeated head trauma — not the actual number of head injuries — and their likelihood of eventually being diagnosed with CTE, but scientists do not know how these traumas add up over the years.

Research into CTE is still in its infancy. One major problem is the small and potentially skewed sample of brains that have been donated to brain banks.

Diagnosing CTE requires a player or their family to elect to donate their brain to science. Therefore, it’s possible that brains with CTE are overrepresented in brain banks because only people with symptoms choose to donate.

One of the most famous CTE cases is that of Dave Duerson, a safety who played in the NFL for a decade.

Duerson sent a text message to his family requesting his brain be sent to Boston University before committing suicide. Duerson was experiencing extreme emotional and cognitive symptoms and thought CTE may have been to blame and was in fact diagnosed with CTE after a postmortem exam of his brain.

However, former athletes who feel healthy may not consider having their brains studied. While the Boston University team has found CTE in nearly all of the NFL players they have examined, this does not mean that all NFL players have CTE.

While CTE is certainly more common in people with a history of playing contact sports than in the general population, it may still only be a small fraction of those athletes.

Research is ongoing to both develop tests for diagnosis during the lifetime of former players, as well as attempts to recruit a broader range of people to donate their brains to brain banks.

Scientists and doctors continue to try to understand the link between concussions and CTE, but there is undoubtedly a strong correlation. Proving causation is often impossible in human studies, so correlation becomes the gold standard. Although research into CTE is ongoing, the results are already clear enough that the NFL’s denial of any links between head injury and subsequent neurodegeneration is irresponsible.

Additionally, an investigation from The New York Times showed that the NFL underreported head injury rates in their own data set of concussions in the NFL, making their statistics on the risk of head injury misleading and artificially low. The NFL does continue to conduct head injury research, but their history of misreporting data calls future conclusions into question.

Recently, Jeff Miller, the NFL Senior Vice President of health and safety policy, did say there was “certainly” a link between playing in the NFL and CTE, but others in the NFL later walked that statement back.

The path forward, both for current and former players, is unclear. Work is being done to reduce the impact of CTE by improving safety equipment to prevent concussions, refining sideline assessments to identify athletes at risk for lasting damage, and developing effective treatments for concussions.

Research is also being done into the development of CTE, including ways to diagnose and treat it during the lives of those who already have a history of head trauma.

The NFL can facilitate research by acknowledging the problem, but that is only the first step of many to better diagnose and treat those affected.

Brain injury research to focus on moderate concussion

Viji Santhakumar, an associate professor of molecular, cell and systems biology at the University of California, Riverside, has received funding from the National Institute of Neurological Disaster and Stroke of the National Institutes of Health to further pursue research on moderate concussive brain injury, which results from car accidents or sports-related concussions.

The more than $2.3 million five-year renewal grant will allow Santhakumar’s lab to study how inflammatory responses after brain injury contribute to the creation of abnormally connected neurons, and whether this compromises critical memory processing functions.

“We expect this research project will provide fundamental insights into how memory deficits and epilepsy develop after brain injury,” said Santhakumar, who joined the UC Riverside faculty in 2018. “It will help us identify potential early therapies to prevent the development of epilepsy as well as memory and cognitive issues after brain injury.”

A concussion is a traumatic brain injury that affects brain function. Usually not life threatening, they can cause serious symptoms requiring medical attention. Generally, concussion has three grades: mild, moderate, and severe.

An expert in epilepsy and traumatic brain injury, Santhakumar explained that the hippocampal dentate gyrus, where new neurons are born well into adulthood, is affected by concussive brain injury. The dentate gyrus plays essential roles in learning and memory, as well as in spatial navigation.

“Here we have an increase in the birth of new neurons after brain injury,” Santhakumar said. “But whether they are helpful or harmful — the excessive burst of new brain cells could lead to epileptic seizures and long-term cognitive decline — is being debated. We will be examining how the excess newly born neurons mature, connect with other neurons, and shape brain activity patterns. We hope to determine how these neurons influence memory processing and development of epilepsy after brain injury and find mechanisms by which we can prevent memory deficits and epilepsy after brain injury.”

The research will be conducted in mice, a model system that has delivered insights in potentially treating several human diseases, including brain injury.

The project, which will likely support two graduate students and a postdoctoral fellow, will examine recordings of brain activity and behavioral outcomes while manipulating the activity of newly born neurons in the normal and injured brain.

“We will examine the role of specific immune receptors, and the pathways by which they alter neuronal birth and maturation,” Santhakumar said. “We will accomplish this by using drugs to block these receptors, which has a potential clinical value and by deleting specific genes in neurons, enabling an examination of specific cell types involved.”

The project, which began April 1, is titled “Contribution of innate immune receptors to neurological dysfunction after traumatic brain injury: Mechanisms and therapeutic implications.”

Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number R01NS097750. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.