Pathophysiology and RTP

An understanding of the pathophysiology of concussion and the cellular dysfunction that occurs guides the approach to an athlete’s eventual RTP. Current understanding of the pathophysiology of concussion supports the neurometabolic cascade theory, which has been well described elsewhere (please see the article by Schrey and colleagues elsewhere in this issue for details). It theorizes that concussions result in microscopic cellular damage and disruption of the normal equilibrium of the cellular membrane. This disruption and axonal stretch causes a cellular depolarization and release of excitatory amino acids and disrupts the ionic balance in the cell. The Na ⁺ /K ⁺ ATP-dependent pump initiates to regain the cell’s normal ionic balance. This energy-dependent, glycolytic pathway eventually leads to lactate accumulation. Ca ²⁺ rushes into the mitochondria and inhibits oxidative processes. These intracellular processes lead to, and are accompanied, by secondary damage to the axonal substructure.

There is an initial hyperglycolysis that occurs immediately after the injury and may last up to 30 minutes. This hyperglycolysis quickly transforms into a glucose hypometabolism that may last for days. In more severe brain injury, there is well-described impaired cerebral blood flow that limits the ability of the cells to acquire more glucose. The increase in the brain’s intracellular demands, combined with a supply-side limitation in glucose, is theorized to lead to the clinical features of concussion. This supply-and-demand mismatch may explain the common complaint that mental and physical exertion exacerbate or uncover symptoms in patients who are asymptomatic at rest.

Epidemiology and RTP

Concussion epidemiology data have been reported for multiple sports, age groups, and competition levels (see the article by Jinguji and colleagues elsewhere in this issue for further details). The highest overall number of concussions occur in men’s football and in women’s ice hockey. Recent data indicate the overall rate of concussion in high school to be 0.23 per 1000 athlete exposures. The collegiate rate is higher at 0.43 per 1000 athlete exposures.

The terms simple and complex are based on duration of symptoms, and the Zurich consensus statement states that these terms have limited usefulness. There is no mechanism to prospectively predict which athletes will have prolonged recoveries, making this distinction of limited value. Discussing recovery timeframes with athletes is reasonable, because 80% to 90% of youth athletes improve within 7 to 10 days. However, all concussions are not equal, and a 3-month recovery is different than a 3-day recovery. It is not yet possible to factor these differences into practical management, and there is a limited amount of information available specifically for recovery from more severe concussions.

Athletes with a history of previous concussion are more likely to have repeat concussions than their nonconcussed counterparts. Athletes with 3 or more concussions are more than 3 times as likely to suffer a concussion than their nonconcussed counterparts. Athletes with a history of more than 3 previous concussions have a more severe sideline presentation, including LOC, anterograde amnesia, confusion, and overall number of symptoms. In a large study of nearly 17,000 high school and collegiate athletes, the rate of repeat concussion within the same season is reported to be 3.8%, and 79.2% of these athletes with second concussions occurred within 7 days of the first concussion. These are compelling data to suggest that even a youth athlete in whom symptoms resolve rapidly should not RTP within 7 days of the initial concussion, although this is not a defined standard of care. There is no current way to predict which athletes are at risk for the repeat first-week concussions.

Modifying factors associated with prolonged PCS include history of depression, mental health disorders, migraine, headache disorder, attention deficit and hyperactivity disorder, learning disability, and sleep disorders. Table 1 summarizes the full spectrum of modifying factors associated with PCS. These modifying factors should be identified in athletes presenting with concussion, but there is no clear way of using them in RTP decisions.

Epidemiology and RTP

Concussion epidemiology data have been reported for multiple sports, age groups, and competition levels (see the article by Jinguji and colleagues elsewhere in this issue for further details). The highest overall number of concussions occur in men’s football and in women’s ice hockey. Recent data indicate the overall rate of concussion in high school to be 0.23 per 1000 athlete exposures. The collegiate rate is higher at 0.43 per 1000 athlete exposures.

The terms simple and complex are based on duration of symptoms, and the Zurich consensus statement states that these terms have limited usefulness. There is no mechanism to prospectively predict which athletes will have prolonged recoveries, making this distinction of limited value. Discussing recovery timeframes with athletes is reasonable, because 80% to 90% of youth athletes improve within 7 to 10 days. However, all concussions are not equal, and a 3-month recovery is different than a 3-day recovery. It is not yet possible to factor these differences into practical management, and there is a limited amount of information available specifically for recovery from more severe concussions.

Athletes with a history of previous concussion are more likely to have repeat concussions than their nonconcussed counterparts. Athletes with 3 or more concussions are more than 3 times as likely to suffer a concussion than their nonconcussed counterparts. Athletes with a history of more than 3 previous concussions have a more severe sideline presentation, including LOC, anterograde amnesia, confusion, and overall number of symptoms. In a large study of nearly 17,000 high school and collegiate athletes, the rate of repeat concussion within the same season is reported to be 3.8%, and 79.2% of these athletes with second concussions occurred within 7 days of the first concussion. These are compelling data to suggest that even a youth athlete in whom symptoms resolve rapidly should not RTP within 7 days of the initial concussion, although this is not a defined standard of care. There is no current way to predict which athletes are at risk for the repeat first-week concussions.

Modifying factors associated with prolonged PCS include history of depression, mental health disorders, migraine, headache disorder, attention deficit and hyperactivity disorder, learning disability, and sleep disorders. Table 1 summarizes the full spectrum of modifying factors associated with PCS. These modifying factors should be identified in athletes presenting with concussion, but there is no clear way of using them in RTP decisions.

Same-day return-to-play

There is consensus that no youth athlete with a concussion should return to play on the same day as the initial injury. Multiple national and international organizations have position statements or clinical papers that support this position, including the National Athletic Trainer’s Association and American Academy of Pediatrics. The AAN has issued a practice reference sheet and is preparing an updated guideline for late 2011. The National Collegiate Activities Association (NCAA) has mandated that schools have concussion management plans and have precluded same-day RTP, stating in their most recent Sports Medicine Handbook that “Student-athletes diagnosed with a concussion shall not return to activity for the remainder of that day. Medical clearance shall be determined by the team physician or his or her designee according to the concussion management plan.”

The current Concussion in Sport consensus statement states that same-day RTP can be considered in select, adult populations in which there is sideline access to experienced physicians, neuropsychologists, neuroimaging, and sideline access to neurocognitive assessment. The National Football League has stated that “Once removed for the duration of a practice or game, the player should not be considered for return-to-football activities until he is fully asymptomatic, both at rest and after exertion, has a normal neurologic examination, normal neuropsychological testing, and has been cleared to return by both his team physician(s) and the independent neurologic consultant.” The principles of asymptomatic RTP are still in effect in this select scenario, and full symptom and cognitive recovery must take place before same-day RTP may be considered. In clinical practice, this scenario is limited to professional sports and an adult population.

Second-impact syndrome

The most devastating complication in sports concussion is second-impact syndrome (SIS). This is a clinical syndrome in which an athlete suffers a concussion and returns to play before the symptoms have resolved. A second traumatic insult occurs, usually involving a smaller impact, and a rapid deterioration in neurologic status is observed, leading to death within minutes from primary cerebral swelling and cerebellar herniation. Imaging and autopsy classically reveal no intracranial bleeding. These clinical factors define SIS. There are increasing numbers of cases that involve a small amount of intracranial bleeding in the presence of massive cerebral swelling. These small hematomas do not account for the severity of the clinical outcomes. Most of the reported cases have been in athletes less than 18 years old, although there are cases of older athletes within the literature.

The rapidity of neurologic decline and the extreme nature of the brain swelling suggest a problem with the brain’s ability to autoregulate, which corresponds with the current understanding of concussion pathophysiology. In a rat mild traumatic brain injury (mTBI) model, all animals received a first mTBI and then a second was induced at intervals of 1, 3, or 7 days after the first. No rat deaths were reported in the control group (single mTBI), whereas 10% of rats died in the double-impact group. In addition, the cellular and mitochondrial changes seen were more significant than those with a single injury. Rat model data suggest that the glucose metabolism may be altered up to 10 days after the initial injury and Ca ²⁺ derangements up to 4 days after single injury, and concerns exist that these time periods may be longer in humans. These animal model findings help support the concept of no same-day RTP, although further research is necessary to help identify the application of this theory in humans.

Probable or definite SIS is exceedingly rare and no true incidence is known. Arguments have been made that RTP protocols are based largely on fear of SIS. The cases of SIS are devastating to families and communities and are highly publicized in the medical and lay press. It is the most severe outcome of concussion and cannot be ignored. There is no evidence to suggest that athletes with a history of multiple concussions have a greater likelihood of SIS, although the small number of reported SIS cases makes this a tentative statement. Nonetheless, there are many more common consequences of premature RTP and early exertion, like prolongation of symptoms and poor neurocognitive performance.

Current RTP protocol

No athlete should RTP while still suffering from symptoms. This recommendation is consistent throughout the literature. The Zurich consensus statement outlines a framework from which to approach an athlete who has recovered from the symptoms of a concussion and is ready to begin working toward a return to competition ( Table 2 ). Each stage should take 24 hours before advancing to the next stage. If athletes experiences a return of their symptoms, they should stop advancing and return to the previous stage. They should remain at the previous stage for 24 hours before attempting the next stage in the RTP protocol. This protocol takes approximately 1 week to complete, assuming that the athlete remains asymptomatic. However, this protocol may take weeks or months to complete depending on the athlete’s response to the increasing exertion.

There is some discussion in the Zurich consensus statement that the elite, adult athlete may RTP more rapidly than the nonelite athlete. This concept was recently echoed by Putukian and colleagues. This idea is based more on access to experienced medical professionals than on a difference in pathology or recovery. For example, a professional or NCAA athlete may have immediate, daily access to a trainer, neuropsychologist, physician, and concussion specialist. This access combined with the high experience level of the medical team may translate into faster RTP. However, this concept of rapid RTP is controversial and currently has no level I evidence to support it. This expedited model of RTP currently has no role for the nonelite, youth athlete.

Athletes who have had prolonged postconcussion syndrome may take longer to progress through these stages, although this may be because of underlying deconditioning from lack of activity rather than a difference in neurocognitive recovery. The provider should be aware of these issues to prevent other injuries from overzealous athletes returning to full competition before they are physically prepared. Athletes who have months of symptoms should start a conditioning and training program similar to athletes with musculoskeletal injuries that require significant loss of participation time.

Neuropsychological data and RTP

Neuropsychological (NP) testing abnormalities are well described in the literature, and the National Academy of Neuropsychology has issued a position paper on the use in concussed athletes. Because the treatment protocols have changed to restrict any symptomatic athlete from returning, the role of NP testing is still debated. Several studies have found that NP abnormalities resolve in parallel with symptom resolution. If this were true in every case of concussion, the usefulness of NP testing might be called into question. There are several other studies that indicate that NP testing may resolve more slowly than symptoms. This would suggest that NP testing offers another degree of assurance that an athlete has fully recovered and can begin an RTP program. Athletes who undergo NP testing tend to RTP more slowly than their nontested counterparts.

NP testing results are not a substitute for clinical judgment and a return to baseline on NP testing is only 1 component of RTP decision making. NP testing becomes increasingly useful as the duration of symptoms expands to track neurocognitive improvement. The neuropsychologist also has the ability to screen for comorbid and preexisting conditions like anxiety, depression, undiagnosed learning disability, and others that may affect clinical decision making and potential interventions. In student athletes, NP testing may help guide school accommodations and help more objectively document cognitive dysfunction. Student athletes who have severely prolonged PCS should have clear medical and NP documentation of their condition as they move forward to prevent problems during the high school or college admissions process.

Psychological considerations

As acute symptoms move into chronic PCS, the interplay of nonorganic, social, and psychological factors becomes increasingly important. Jacobson discusses the issues of physiogenesis and psychogenesis as they relate to PCS. Premorbid mental and physical health status were more predictive of persistent PCS than head injury severity (as defined by LOC and posttraumatic amnesia) in a study of adults with mild TBI. PCS has also been described as an environmental stress combined with an individual predisposition to the injury or syndrome. Preconcussion depressive symptoms may alter baseline neuropsychological testing. Interventions to help an athlete address these issues include consulting a sports psychologist, biofeedback, visualization exercises, support groups, and reintegration into social groups.

Recovery from sports injuries are classically believed to follow the stages of grief hypothesized by Kübler-Ross, including denial, anger, bargaining, depression, and acceptance. The grief model in athletes tends not to involve the denial stage prominently. Wiese-bjornstal and colleagues created a model to identify the factors affecting an athlete with a sports injury. A comparison study between athletes with anterior cruciate ligament (ACL) injuries and concussion found that both groups had increased depression scores. The ACL group had more significant and longer-lasting changes. The concussed group had depression scores that lasted approximately 1 week and a more severe total mood disturbance at day 4. This finding may reflect that the depression experience by the acutely concussed athlete is a direct result of the concussion, rather than a situational depression. There is significant overlap between the symptoms of depression and those of PCS as shown by Iverson who found that almost 50% of depressed patients without current concussion endorsed symptoms at a clinically significant level for PCS as defined by the DSM-IV. Alternative diagnoses must be ruled out to decrease attribution error (ie, all subsequent symptoms attributed to the concussion). To some extent, stigma still surrounds anxiety and depression and it may be more socially acceptable for an athlete and/or their families to attribute symptoms to a sports injury rather than to an underlying psychiatric condition.

In the professional athlete, these issues include the concern of loss of livelihood. Media exposure of the injury adds to the pressure on both the athlete and the treating physician to return an athlete as quickly as possible. As with all team physicians, the primary responsibility is to athletes and their health.

Athletes returning to play face several issues not directly related to their concussion. These issues commonly include fear of repeat concussion, concern for future disability, and performance anxiety. Many athletes suffer from the loss of a sense of invincibility and decrease in overall health during the recovery from concussion. Isolation and lack of social support during the removal from practice and play is a common stressor for concussed athletes. There is increasing awareness about the role of anxiety and depression as direct sequelae of concussion. Concern exists that the treatment of concussion (prolonged rest) may lead to depressed mood, fatigue, and irritability. Aerobic, anaerobic, and resistance exercise have beneficial mood effects and alter the brain’s neurochemistry. The removal of exercise combined with the cascade of neurometabolic changes may exacerbate these mood disturbances. Athletes in whom low-grade symptoms linger for several weeks may consider a trial of gentle aerobic exercise in efforts to remove these iatrogenic causes for prolonged PCS. A recent preliminary safety study on concussed patients with more than 6 weeks of symptoms using an incremental treadmill protocol showed that the athletes were able to exercise at near age-predicted heart rate maximum without symptom exacerbation. The patients had symptom improvement that corresponded with their peak heart rate. This study is promising but small (n = 12). Larger numbers of patients and reproducible results are needed before expanding this to nonexperimental populations. Athletes should not be returned to a contact situation until they are fully asymptomatic.

It is wise to discuss these issues proactively with an athlete as they are beginning their RTP protocols and intervening early to limit any undue psychological distress that an athlete may encounter.