Long-term effects of postconcussion syndrome

The symptoms of a concussion may take some time to resolve, resulting in significant long-term burden. When the symptoms of concussion persist as a variety of cognitive, somatic, and behavioral changes, these lingering deficits comprise postconcussion syndrome (PCS). PCS is defined by the International Classification of Diseases, 10th Revision (ICD-10) as the occurrence within 1 month of injury of at least 3 of the 8 symptom categories listed in Box 1 . The Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revised) (DSM-IV-R) requires the presence of symptoms in at least 3 of 6 categories for at least 3 months after injury in addition to evidence of neuropsychological dysfunction, as outlined in Box 2 . Whether PCS is experienced following an mTBI seems to be dependent on a combination of factors, including premorbid vulnerability, postinjury psychological adjustment, and postinjury changes in brain function. While most of these symptoms typically resolve within a few days or weeks following mTBI or other head injury, some individuals suffer from PCS for months or longer and, although studies remain conflicting, it is believed that as many as 15% of people with a history of mTBI still suffer from deficits 1 year after injury.

Adults with PCS often initially present with physical symptoms such as dizziness and headache in the first weeks following injury, with psychosocial symptoms such as depression and irritability first appearing up to a month later. These findings mimic those of rodent models, which have reported both impaired learning and depressive-like behavior in mice following mTBI, perhaps mediated by apoptotic cell death. In addition, single and repeated concussions in adults have been shown to be correlated with cognitive deficits months following the injury. Executive functioning impairment also appears to persist, with adults who had experienced an mTBI 6 months prior found to have significantly decreased information processing speed. At 1 year after injury, the most common symptoms appear to be a combination of the physical, the psychosocial, and the cognitive, with reports of headaches, dizziness, disturbances of senses, light and noise sensitivity, and various psychiatric symptoms, including depression, anxiety, coping issues, and psychosocial disability. In addition, studies have suggested that women are more likely to develop PCS, in terms of both more symptoms reported and a longer duration of impairment.

Some adults continue to show motor deficits, functional deficits, and persistent depressive symptoms more than 1 year after injury. The data here are conflicting, however, with other studies indicating that neuropsychological deficits appear to resolve by 1 year after injury. These latter studies tend to include all individuals who had been exposed to any mTBI rather than just those who experienced PCS symptoms; as a result, the sample is overly dilute and the resulting lack of association is not surprising.

Of interest, several studies have looked at how beliefs regarding expected outcome in response to brain injury might influence an individual’s risk of developing PCS. One study found that individuals who had suffered an mTBI and who indicated that they believed their symptoms would have serious negative consequences on their lives were significantly more likely to experience PCS at 3 months following the injury. In fact, these beliefs regarding the perceived severity at the time of injury were more predictive of PCS symptoms at 3 months than were the total number of PCS symptoms reported immediately following the injury. Another study evaluating attitudes surrounding injury recovery found that self-ratings of PCS symptoms were positively related to emotion-focused coping strategies and negatively related to problem-focused coping in adults who had experienced an mTBI. These findings suggest that one’s attitudes can influence the extent to which a concussion has long-term, persistent effects.

Although PCS is considered to be fully recoverable with proper treatment, suffering from PCS-related symptoms for an extended time may delay an individual’s return to work, adversely affect one’s quality of life, and result in additional social and economic costs. The deficits caused by these symptoms may also have an indirect long-term effect by exacerbating a preexisting depression or impairing the ability to adequately cope with stress. In addition, there is some evidence that concussions result in chronic motor and neuropsychological changes over 3 decades following injury ; however, these findings may be attributable to an early-stage neurodegenerative disease associated with concussion, as discussed later.

Although studies and diagnostic criteria of PCS initially reported dissimilar symptoms for adult and pediatric populations, it is now acknowledged that children and young adults report a PCS that is similar to adults and may suffer from the same behavioral, emotional, and somatic difficulties following mTBI. Many of these initial studies of youth concussions focused on athletes, as they tend to be at increased risk of experiencing concussions. Although college football athletes report a higher incidence of concussion than high school athletes, it has been reported that high school athletes take longer to recover, based on neuropsychological testing. This finding of increased youth susceptibility to PCS has been extended to other sports and activities, and is perhaps explained by the fact that the frontal lobes do not fully develop until late adolescence. Rodent models have also suggested that the immature brain is more susceptible than the adult brain to apoptosis following mTBI. In fact, one prospective cohort study found that age at the time of injury and extent of extracranial injury were the two strongest independent predictors of functional outcome at 6 months after injury. Even in young adults well enough to enroll and continue in college, there is evidence that PCS symptoms may last for years, and that there may be gender differences in PCS resolution, with women reporting more lingering mood and anxiety symptoms.

Children differ significantly from adults and adolescents not only in size but also biomechanically, pathophysiologically, neurobehaviorally, and developmentally. Because the developing brain is more plastic than the mature brain, younger age at the time of injury was originally thought to have a beneficial effect on recovery and expected outcome. However, current literature indicates that this is not the case; the developing brain appears, in fact, to be more vulnerable to diffuse brain injury. Traumatic injury to the immature brain results in a prolonged period of pathogenesis in both cortical and subcortical structures, leading to progressive neurodegeneration, hyperactivity, and sustained cognitive impairments.

Although early studies showed either a small or no effect of head injuries on the developing brain, many of these studies had flawed designs; less than half of the 56 studies reviewed by Satz and colleagues from 1970 through 1998 met even 4 of the 6 following recommendations for methodologically sound studies: (1) the inclusion of control groups (either with no injury or with other body injury); (2) the use of a longitudinal design with follow-up assessment post injury; (3) a clear definition of mild injury, without the inclusion of children with more severe injuries; (4) the inclusion of at least 20 children with mTBI; (5) the use of standardized tests to measure outcomes; and (6) controls for preinjury risk factors.

The most methodologically sound studies have found that children report worse cognitive symptoms more than 1 year after concussion than adults. These deficits are first reported months after the original injury and affect the child’s school work or abilities to function at home. Children aged 6 to 12 years with mTBI have impaired executive functioning and attention 1 year after injury compared with noninjured controls. An mTBI may also cause linguistic changes that adversely affect Verbal IQ and expressive language. Of note, although these deficiencies improved by 6 months after injury, no additional improvement was observed between 6 and 24 months. In such cases where symptoms persist, PCS may adversely affect a child’s conduct and personality, and can lead to extended school absence and limitations on athletic play. In fact, one study reported that children who showed more PCS symptoms displayed worse overall adjustment in comparison with children with fewer PCS symptoms. It has also been suggested that individuals with higher cognitive ability have better outcomes following head injury, because they may be able to recruit alternative and additional neural substrates to compensate for tissue damage.

Although animal models have elucidated the general pathophysiology responsible for acute concussive symptoms, the underlying cause of sustained PCS remains a matter of debate. However, several pathologic mechanisms have been proposed. Some make the pathophysiologic case that a contributing factor for sustained PCS is the microstructural damage of the brain from head injury. Given that the acute injury causes the aforementioned pathophysiologic cascade, it is not unlikely that some of the resulting microstructural damage can persist in some cases and result in the persisting symptoms of PCS sometimes observed. However, as already mentioned for mTBI in adults, the correlation between increased risk of sustained PCS in children with negative coping strategies or beliefs about their mTBI symptoms indicates that there may also be a psychopathologic cause to this long-term PCS.

This matter is further complicated by various methodologic shortcomings in mTBI and PCS research. These limitations may include retrospective, cross-sectional designs, a lack of appropriate control groups, and a failure to separate different degrees of PCS. In addition, studies rely heavily on the self-report of postconcussive symptoms by patients; this has a history of being unreliable, and studies show that a patient’s self-report may be the result of simple malingering, an involvement in litigation, or recall biases such as the “good old days” bias, the idea that individuals who sustain an injury often underestimate problems preinjury. Finally, whereas PCS is an acknowledged condition, there is a disagreement between ICD-10 and DSM-IV diagnostic criteria; this disagreement emphasizes the confusion over the underlying cause of long-term PCS. Whereas the ICD-10 criteria classifies PCS as symptoms without neuropsychological impairment and focuses instead on premorbid conditions and postinjury psychological adjustment, the DSM-IV criteria do require this neuropsychological impairment and seem to assume that PCS and related symptoms are at least partially caused by an underlying brain trauma. The variability in diagnostic criteria, and the assumptions about PCS that this variation implies, result in different incidence estimates and limited diagnostic agreement when dealing with PCS patients.

The enduring effects of PCS appear to be a combination of the biologic, the physiologic, the psychological, and the social. For both the pediatric and adult population, future research that incorporates genetics, advanced neuroimaging, refined cognitive and postconcussive symptom measures, and social environment research can help to achieve an integrated “biopsychosocial” model that may aid in the management of long-term PCS. This, along with effective education and rehabilitation of patients, will work to reduce the incidence and burden of long-term PCS in TBI patients.

Effects on behavior

Having sustained a previous concussion may alter a child’s long-term developmental trajectory years after the symptoms of PCS subside. Studies of PCS typically only follow children for up to 1 year after injury, potentially before the full effects of the injury have manifested themselves. As a result, these studies are unable to measure the extent of the long-term detrimental effects of an mTBI on the developing brain. To properly evaluate the long-term consequences of youth concussion, studies must examine cognitively mature individuals who previously experienced a concussion in their youth.

Because the prefrontal cortex is one of the last brain structures to mature, it is not surprising that parents report attention deficits, hyperactivity, or conduct disorder following a head injury to their child. In addition, it has been shown that the number of long-term neurobehavioral symptoms in children is related to the severity of the initial mTBI as well as the child’s neuropsychological functioning, academic performance, emotional adjustment, and adaptive functioning.

The majority of previous studies examining the effects of brain injuries on development years after the injury have focused on more severe injuries. However, these studies of moderate and severe TBI suggest a specific window of time during which the brain may be more vulnerable to injury; TBI experienced in middle childhood and later appears to be less detrimental than injuries sustained earlier.

One cohort study of 490 children who experienced an mTBI before age 14 years, and who had no prior history of psychiatric illness, found that these children were significantly more likely to have psychiatric issues in the 3 years following injury than were uninjured controls. The children most commonly presented with attentional problems in the first year following injury. However, there was no difference observed in children who had already had a prior history of psychiatric illness in the year preceding the injury.

These studies are complicated by the fact that the children more likely to experience concussions were also more likely to have undiagnosed psychiatric issues. To circumvent this issue, some studies have used detailed retrospective questionnaires to assess preinjury psychiatric status. One prospective longitudinal study found that children who experienced an mTBI requiring hospitalization before age 10 years displayed increased hyperactivity/inattention and conduct disorder between the ages of 10 and 13 compared with children who had not experienced an mTBI, as rated both by their mothers and their teachers. This cohort has been followed through age 16, and these issues have been shown to persist. However, these children did not display any deficits in intelligence or academic skills. In addition, children whose injuries did not require hospitalization showed no differences from control children without a history of mTBI. Although there were differences observed in hyperactivity/inattention and conduct disorder based on age at the time of injury (those injured between 0 and 5 years old and those injured between 5 and 10 years old), these differences were not statistically significant. A later study confirmed these findings and also reported that children injured in preschool had progressively worsening parent and teacher ratings of hyperactivity/inattention and conduct disorder when followed longitudinally from age 7 to 13 years. Another study of 45 adults, with an average age at injury of 8.9 years (standard deviation of 3.3), found that those who experienced posttraumatic amnesia for at least 30 minutes had statistically significant decreases in measures of attention and memory more than 2 decades later. These attentional findings are not surprising, as the prefrontal cortex does not fully develop until late adolescence. In addition, these deficits were not observed in individuals injured as adults.

The effects of mTBI on children do not always end with the resolution of PCS, but may have long-term effects on cognitive processing, mood, and behavior. These delayed behavioral impairments suggest the need for continued monitoring and intervention in children, even years after initial concussion.

Effects on behavior

Having sustained a previous concussion may alter a child’s long-term developmental trajectory years after the symptoms of PCS subside. Studies of PCS typically only follow children for up to 1 year after injury, potentially before the full effects of the injury have manifested themselves. As a result, these studies are unable to measure the extent of the long-term detrimental effects of an mTBI on the developing brain. To properly evaluate the long-term consequences of youth concussion, studies must examine cognitively mature individuals who previously experienced a concussion in their youth.

Because the prefrontal cortex is one of the last brain structures to mature, it is not surprising that parents report attention deficits, hyperactivity, or conduct disorder following a head injury to their child. In addition, it has been shown that the number of long-term neurobehavioral symptoms in children is related to the severity of the initial mTBI as well as the child’s neuropsychological functioning, academic performance, emotional adjustment, and adaptive functioning.

The majority of previous studies examining the effects of brain injuries on development years after the injury have focused on more severe injuries. However, these studies of moderate and severe TBI suggest a specific window of time during which the brain may be more vulnerable to injury; TBI experienced in middle childhood and later appears to be less detrimental than injuries sustained earlier.

One cohort study of 490 children who experienced an mTBI before age 14 years, and who had no prior history of psychiatric illness, found that these children were significantly more likely to have psychiatric issues in the 3 years following injury than were uninjured controls. The children most commonly presented with attentional problems in the first year following injury. However, there was no difference observed in children who had already had a prior history of psychiatric illness in the year preceding the injury.

These studies are complicated by the fact that the children more likely to experience concussions were also more likely to have undiagnosed psychiatric issues. To circumvent this issue, some studies have used detailed retrospective questionnaires to assess preinjury psychiatric status. One prospective longitudinal study found that children who experienced an mTBI requiring hospitalization before age 10 years displayed increased hyperactivity/inattention and conduct disorder between the ages of 10 and 13 compared with children who had not experienced an mTBI, as rated both by their mothers and their teachers. This cohort has been followed through age 16, and these issues have been shown to persist. However, these children did not display any deficits in intelligence or academic skills. In addition, children whose injuries did not require hospitalization showed no differences from control children without a history of mTBI. Although there were differences observed in hyperactivity/inattention and conduct disorder based on age at the time of injury (those injured between 0 and 5 years old and those injured between 5 and 10 years old), these differences were not statistically significant. A later study confirmed these findings and also reported that children injured in preschool had progressively worsening parent and teacher ratings of hyperactivity/inattention and conduct disorder when followed longitudinally from age 7 to 13 years. Another study of 45 adults, with an average age at injury of 8.9 years (standard deviation of 3.3), found that those who experienced posttraumatic amnesia for at least 30 minutes had statistically significant decreases in measures of attention and memory more than 2 decades later. These attentional findings are not surprising, as the prefrontal cortex does not fully develop until late adolescence. In addition, these deficits were not observed in individuals injured as adults.

The effects of mTBI on children do not always end with the resolution of PCS, but may have long-term effects on cognitive processing, mood, and behavior. These delayed behavioral impairments suggest the need for continued monitoring and intervention in children, even years after initial concussion.

When to retire after a concussion

Following a concussion, the absolute contraindications to return to a contact/collision practice or competition sport include:

• 1.
  

  Abnormal neurologic assessment

  
  
• 2.
  

  Symptomatic of postconcussion signs/symptoms at rest or exertion

  
  
• 3.
  

  If done, neuropsychological battery not baseline or above

  
  
• 4.
  

  If done, head computed tomography or MRI shows a lesion placing the athlete at increased risk of head injury (edema, hemorrhage, hydrocephalus, cavum septum pellucidum, arachnoid cyst).

The relative contraindications to return to collision practice or competition include:

• 1.
  

  Postconcussion symptoms that last many months and not days

  
  
• 2.
  

  Mild or indirect blows (whiplash) that produce significant and lengthy postconcussion symptoms.

Thus there are absolute and relative indicators for retirement. Neither are based on a particular number of concussions, but rather on the athlete’s response, including duration of symptoms and ease of being concussed. Keeping in mind the increased vulnerability of the developing brain, it is suggested that one might be even more conservative in the under-18 age group as compared with adults.

Degenerative disease

Brain trauma has long been thought to play a role in initiating or accelerating the molecular cascade involved in several degenerative diseases, including Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS). In addition, repetitive concussive and subconcussive brain trauma has been implicated as the primary risk factor for developing the progressive neurodegenerative disease chronic traumatic encephalopathy (CTE), as well as the motor neuron disease variant chronic traumatic encephalomyelopathy (CTE-M).