The multifaceted characteristics of traumatic brain injury (TBI) complicate the evaluation of therapeutic interventions, including rehabilitation. The intensity, direction, and duration of external forces that cause TBI, coupled with a range of factors specific to the individual and early medical management, affect the pattern and extent of damage and the degree of recovery (Maas et al. 2008). These combined factors may determine the type and effectiveness of the rehabilitation therapy. In this chapter, the pathophysiology of TBI, injury complications, and person-specific variables are discussed in relation to outcome. Chapter 3 addresses other factors related to recovery after TBI. These chapters provide the relevant background for interpreting the cognitive and neurobehavioral sequelae of TBI. Research indicates that TBI may manifest differently depending on the mechanism of injury. For example, blast-induced neurotrauma (BINT) shows significantly more changes in brain matter versus TBI caused by other forces. Because active duty members of the military and veterans have higher exposure to blasts than civilians, TBI incurred by military and veteran populations may determine different outcomes than non-blast-related TBI. However, civilians may be exposed to blasts due to terrorism, occupational hazards, or other acts of violence. The committee assumes civilian versus military populations respond similarly to TBI, unless otherwise noted.
TBI causes both direct, immediate physical damage and delayed, secondary changes that contribute to subsequent tissue impairment and related neuropsychiatric dysfunction. Injury may be focal or diffuse; due to closed impact or penetrating insults; and if severe, may include other complicating factors such as hemorrhage, hypoxia, reduced blood flow, or metabolic
alterations (Jeremitsky et al. 2003; Saatman et al. 2008). These early, acute events are highly relevant to long-term outcomes, as they can critically affect an individual’s degree of disability and need for rehabilitation. The following chapter does not contain exhaustive descriptions of the many factors related to TBI. The reader may refer to Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury (IOM 2009) for more in-depth discussion of TBI biology.
The response to injury and subsequent treatment varies by multiple factors unique to the affected individual, such as age, gender, genetics, cognitive reserve, polytrauma, multiple concussions from the same impact, and history of prior brain injury (Colantonio et al. 2008; Loane and Faden 2010; Perel et al. 2008). Such variability influences long-term functional outcomes, including cognitive processes. The ultimate degree of recovery likely reflects individual variability with regard to neuroplasticity, or the ability of undamaged brain regions or pathways to take over irreparably damaged cells or brain regions (Cramer et al. 2011). Although most mild injuries appear to recover completely within weeks to months after trauma, a small but not insignificant subset of mild TBIs cause longer-term symptoms, and these also may be associated with sustained or progressive neuroimaging abnormalities (Vannorsdall et al. 2010). Secondary injury processes may continue for months or years, particularly with moderate or severe injuries, which may lead to progressive long-term tissue loss (Greve and Zink 2009; Werner and Engelhard 2007). Thus, characteristics of the injury and the individual contribute to the heterogeneity of TBI, which has implications for treatment options.
Head injuries have historically been classified using various clinical indexes that include pathoanatomical features, severity of injury, or the physical mechanisms of the injury (i.e., causative forces). Different classification systems may be used for clinical research, clinical care and management, or prevention. Additional classification schemes include those that address secondary injury. The classification systems most relevant to rehabilitation help determine pace of recovery or expected degree of impairment. These systems include the Glasgow Coma Scale (GCS), posttraumatic amnesia (PTA), duration of loss of consciousness (LOC), and degree of altered consciousness.
Sometimes known as the “where and what” of TBI classification, pathoanatomical classification describes the location and the pathological
features (i.e., pathoanatomy) of tissue damage induced by the injury. Pathoanatomical features influence outcomes for individuals with brain injuries (Saatman et al. 2008) and indicate the likelihood of developing certain secondary problems (e.g., cerebral edema) (Saatman et al. 2008). Pathoanatomical classification may aid with prognosis (Saatman et al. 2008), which helps determine the appropriate timing and type of rehabilitation. The injury is classified based on the presence or absence of a mass lesion, which is found using diagnostic tools such as computed tomography (CT) and magnetic resonance imaging (MRI) (Olson-Madden et al. 2010). Imaging helps with location of injury, which can be useful in understanding localization of deficits (e.g., frontal lobe injuries are associated with problems with attention, initiating activity) (Kringelbach and Rolls 2004).
Severity of TBI is generally graded from mild to moderate or severe. Severity can be classified in multiple ways, and each measure has different predictive utility, including determining morbidity, mortality, or long-term functional outcomes. Patients with more severe head injuries demonstrate lower cognitive functioning and have more gradual cognitive improvements following the initial injury (Novack et al. 2000). Degree of severity is often based on the acute effects of the injury, such as an individual’s level of arousal or duration of amnesia, and these are measured by the GCS, PTA, duration of LOC (Ptak et al. 1998) and degree of altered consciousness.
The majority of TBIs are mild, consisting of a brief change in mental status or unconsciousness. Mild TBI is also referred to as a concussion. While most people fully recover from mild TBI, individuals may experience both short- and long-term effects. Moderate-severe TBI is characterized by extended periods of unconsciousness or amnesia, among other effects. The distinction between moderate and severe injuries is not always clear; as such, individuals with moderate and severe injuries are often grouped for research purposes. Throughout the remainder of this report, the committee refers to more severe injuries as moderate-severe TBI. Chapter 1 provides epidemiological statistics on TBI by severity.
These classification systems not only determine the severity of TBI, but also may be indicative of the degree of long-term disability. The more severe the injury, the more severe and persistent the cognitive deficits—though clinical measurements do not always concur. Severity measures graded during the acute phase sometimes reflect variance due to medications used during resuscitation, substance use, and communication issues. However, the relationship between clinical severity measures (e.g., GCS, LOC, and PTA) and various types of outcome measures (e.g., neuropsychological, functional disability, levels of handicap) has been well established (Cifu et
al. 1997; Dikmen et al. 2003; Sherer et al. 2002; Temkin et al. 2003). The utility of these measures depends on factors such as how long after the injury a patient is evaluated. Measures obtained later in time are generally better predictors of long-term outcomes; specifically, duration of PTA is more predictive than duration of LOC, which is more predictive than GCS at the time of injury (Katz and Alexander, 1994). Table 2-1 includes the mild, moderate, and severe classifications.
The most common classification scheme for TBI injury severity is the GCS, which has been in use since the 1970s. It provides a numerical index of level of consciousness that is used to grade injury severity. The 15-point scale is based on ratings of eye opening, verbal behavior, and motor behavior (Teasdale and Jennett 1976). A score of 13 to 15 is classified as mild, 9 to 12 as moderate, and 3 to 8 as severe. Though well known and widely used, this classification scheme is most useful in predicting acute survival and gross outcome, and performs more poorly in predicting later and more detailed functional outcomes, particularly in cognitive and emotional realms. Valid scoring has also become more difficult with earlier intubation and sedation for individuals with more severe injuries. However, more recent studies have found that the motor component of GCS may be more useful in predicting outcomes than the verbal data, which has not been found useful (Healey et al. 2003).
Other postinjury conditions contribute to the spectrum of severity, such as posttraumatic amnesia. PTA is defined as the interval between injury and return of day-to-day memory. It is a state of confusion that occurs immediately following TBI, in which the injured person is disoriented and unable to remember events after the injury. PTA can be directly assessed during the subacute stage of recovery using a brief examination that tests orientation and memory for circumstances of the injury and events prior to and following the injury. In addition, duration of PTA can be estimated retrospectively by asking the patient memory-related questions concerning
|Severity of Injury/Measure||Mild||Moderate||Severe|
|Glasgow Coma Scale||13 to 15||9 to 12||3 to 8|
|Loss of Consciousness||< 30 minutes||> 30 minutes
< 24 hours to 24 hours
|> 24 hours|
|Posttraumatic Amnesia||< 24 hours||> 24 hours
|≥ 7 days|
|Altered Consciousness||≤ 24 hours||> 24 hours||> 24 hours|
SOURCES: Helmick et al. 2007; Kay et al. 1993.
events immediately postinjury and estimating the postinjury interval prior to restoration of memory. In contrast to the brief duration of PTA after mild TBI—typically 5 to 10 minutes and less than 30 minutes—PTA could extend for days to weeks after severe TBI. Beginning rehabilitation prior to the end of PTA may be problematic since the patient is less likely to transfer learning across sessions.
Retrograde amnesia may also be present after injury, but its duration is typically shorter than PTA. Retrograde amnesia is “partial or total loss of the ability to recall events that have occurred during the period immediately preceding brain injury” (Cartlidge and Shaw 1981). In contrast, anterograde amnesia is difficulty forming new memories after the trauma, and it can sometimes lead to a decreased attention span and inaccurate perception. After a loss of consciousness, anterograde memory is often one of the last cognitive functions to return (Cantu 2001).
Natural History of Recovery
The natural process of recovery following TBI depends upon the initial injury severity, as described with the GCS, though there can be considerable variability even within categories. With most injuries there is a gradual resolution of symptoms. For most mild, single concussive injuries, the majority of patients are symptom-free within several weeks (Belanger and Vanderploeg 2005; Carroll et al. 2004; Lovell et al. 2003; McCrea et al. 2003). Several meta-analyses indicate the path to preinjury symptom levels following a mild TBI is 2 weeks, approximately, and no more than 3 months (Iverson 2005; McCrea et al. 2009). Development of new symptoms following resolution of the initial symptoms in civilians with mild TBI occurs infrequently. However, with multiple mild TBIs, both the number and duration of symptoms are likely to increase.
The course of recovery from severe TBI is more prolonged, with greatest function recovery occurring within 1 to 2 years of injury. One study (Corrigan et al. 1998) reported that following rehabilitation, an increasing number of people were independent at 6 to 12 months, and up to 5 years, postinjury. In another study assessing recovery in people with severe TBI, approximately 22 percent of individuals were found to have improved from year 1 to year 5; however, 14 to 15 percent declined, and approximately 62 percent remained unchanged (Millis et al. 2001). At the present time, the course and pattern of recovery following blast-related TBI is not well characterized, with no published longitudinal studies. However, the congressionally mandated Longitudinal Study on Traumatic Brain Injury Incurred by Members of the Armed Forces in Operation Iraqi Freedom and Operation Enduring Freedom (H.R. 5122) is currently ongoing and should provide details on the natural recovery in this population.
Heterogeneity of the injury is important to consider because it may help determine those who will benefit from cognitive rehabilitation therapy (CRT). Participation in CRT generally requires patients to be stable and recovered well enough to participate effectively in goal-oriented treatment programs. This generally occurs after the acute care phase. The unique, heterogeneous nature of an individual’s TBI should be taken into account when designing or delivering a CRT program. Some of the most important heterogeneous factors to consider are physical mechanisms, pathobiology, severity, presence of polytrauma, multiple impacts, and other factors including age, gender, cognitive reserve, and genetic variation.
Physical Mechanisms of Injury
The physical mechanism of TBI, which determines the forces involved in the injury, represents an alternate way of classifying head injury based on the causative forces of the injury. Injuries can be classified according to whether the head makes contact with an object (also called impact loading) and whether the brain moves within the skull due to acceleration or deceleration forces (inertial loading) (Gennarelli 1983). Lesions can form when the brain is brought into contact with the skull, when an object strikes the head, or as a result of acceleration or deceleration. Medical records often only indicate the acute injury classification of a trauma, not its cause. This challenge must be overcome in clinical practice, where the event’s preceding conditions must be estimated from incomplete details (Saatman et al. 2008). In addition to severity, anatomical features of the injury (i.e., pathobiology) and the mechanism of causative forces are important factors to consider, especially for rehabilitation purposes, as explained in the following sections. Mechanisms of injury may manifest in different ways, and include focal versus diffuse injuries as well as penetrating versus closed head injuries. Another way to characterize the physical mechanisms of TBI is to compare those that are commonly seen in military populations with those most commonly seen in civilian populations. These physical mechanisms of injury may occur in various combinations.
Focal Versus Diffuse
Whether an injury is focal, diffuse, or both contributes to the degree of heterogeneity of the resulting damage. A focal injury refers to a wound at a specific location, which affects the grey matter of the brain; a diffuse injury refers to more widespread damage, causing degeneration of white matter. Focal injuries most commonly reflect cerebral contusion resulting
from impact, with or without a fracture to the skull (Povlishock and Katz 2005). Features of focal injury may include lacerations, contusions, and/or hemorrhage (Morales et al. 2005). Diffuse injuries often result from rapid rotations of the head, which cause tissue distortion, typical in automobile accidents. Diffuse axonal injury, now superseded by the term traumatic axonal injury (TAI), can occur with either focal or diffuse brain injury, most commonly following rapid acceleration or deceleration of the head. TAI, which is often caused by blasts (Mac Donald et al. 2011), is characterized by shearing forces that cause axonal stretching, often with swelling of the brain and fiber degeneration. TAI can serve as a predictor of outcome (Graham et al. 2002; Hurley et al. 2004), though the long-term implications on treatment in humans are still not well understood (Greer et al. 2011).
Focal and diffuse injuries also may occur in combination (Povlishock and Katz 2005), which is often the result of a penetrating brain injury caused by severe whiplash or blast (Hynes and Dickey 2006); these features are commonly seen in military wounded with moderate-severe TBI. Blunt injuries can be either focal or diffuse—or, in some cases, mixed. Both static and dynamic forces cause blunt head injuries. Static loading occurs in crush-type injuries (e.g., avalanche, landslide) and is relatively uncommon (Graham et al. 2006). This type of injury generally causes skull fracture, and in more severe cases can cause brain laceration and coma. More often, blunt force injuries to the head are caused by dynamic forces: direct impact or rapid acceleration, deceleration, or rotational movement, which significantly strain the brain tissue (Graham et al. 2006).
Penetrating Versus Closed
Penetrating injuries involve an object entering or lodging within the cranial cavity. In civilian populations, these most often result from projectile or knife wounds; in the military setting, blast-related shrapnel or missile injuries are the most common causes (Warden 2006). Penetrating injuries have been less studied than closed models. Closed head injuries occur due to a nonpenetrating injury to the brain, usually resulting from a rapid rotation or shaking of the brain within the skull, or by impact to the skull. The most frequent causes of closed head injury are motor vehicle accidents or falls, resulting in either diffuse or focal injury. When not accompanied by penetrating wounds, a blast may also cause closed head injury. Common symptoms of nonpenetrating TBI include TAI, contusion, and subdural hemorrhage.
Military Versus Civilian
TBI has been the signature injury in the conflicts in Afghanistan and Iraq (Operation Enduring Freedom [OEF] and Operation Iraqi Freedom
[OIF]), with blast-induced neurotrauma (BINT) the most common cause due to increased use of improvised explosive devices (IEDs). It has been estimated that approximately 22 percent of military personnel in these war zones may sustain a TBI, and that as many as 60 percent of injured soldiers may have a TBI as part of their clinical spectrum (Terrio et al. 2009). Previous military campaigns have seen much lower rates of TBI-related injuries and mortality. In the Vietnam War, approximately 40 percent of the 58,000 U.S. combat fatalities were due to head and neck wounds and 14 percent survived a head injury (Schwab et al. 2003). In 1991, only about 20 percent of the military wounded in Operation Desert Storm were treated for head injuries (Carey 1996; Leedham and Blood 1992). The mortality and morbidity patterns during the OIF/OEF years still await full analysis.
BINT is often mild and may occur in combination with physical injuries, which may mask symptoms of TBI, causing true incidence to be underestimated. While body armor improvements have increased survival rates, they may also increase TBI prevalence either by preventing death from organ trauma or by potentially reflecting the blast waves (Phillips et al. 1988; Warden 2006). Blast injuries themselves are highly heterogeneous, and may result in primary, secondary, tertiary, quaternary, or quinary effects. Injuries that occur as a direct result of blast wave–induced atmospheric pressure changes, also called barotraumas, are referred to as the primary blast injury; these injuries may result in organ and tissue damage due to the forces of acceleration and deceleration. Secondary injuries may occur from the impact of blast-energized debris, producing penetrating or nonpenetrating injuries. Tertiary injuries can result from the blast victim being thrust against an immovable object, such as a wall or heavy machinery. Quaternary injuries can come from exposure to heat or fire generated by the blast. Quinary injuries may result from exposure to toxic agents released by the blast. In the military population, exposure to multiple blast injuries is common and may increase subsequent TBI-related symptoms and disability (Belanger et al. 2009). A recent study of active duty military with primary blast exposure plus another blast-related mechanism of injury (e.g., a motor vehicle collision or being struck by a blunt object) demonstrated the unique nature of military blast TBI (Mac Donald et al. 2011). The study found that patients demonstrated substantial numbers of abnormalities in the brain; civilian cases consistent with TAI do not commonly share these abnormalities. Although BINT may be unusually high compared to head injuries sustained by civilians, the risk of exposure to explosive devices exists in nonmilitary settings due to landmines, explosive weaponry used in terrorist incidents, or industrial or recreational accidents (Bilukha et al. 2008). Blast-related injuries are only in the beginning stages of study; pending
development of further research, the true impact of these injuries on short- and long-term outcomes for survivors are unknown.
As detailed above, the consequences of TBI depend in part on which areas of the brain are injured. The “primary injury,” not to be confused with primary blast injury, refers to the immediate mechanical damage to brain cells and tissue that occurs at the moment of impact. This damage is nonreversible and therefore untreatable. In contrast, “secondary” or delayed injury occurs after the trauma and may progress for days, months, or even years; the damage from this injury is potentially treatable. Secondary injury is a complex, multifactorial process that includes metabolic and physiological changes related to biochemical alterations at the molecular and cellular level. In addition, secondary insults, such as hypoxia, hypotension, hypercarbia, and hyponatremia have long been recognized as influencing the outcome of TBI. It is well known that chronic inflammation occurs after TBI, but recent experimental and clinical studies indicate that persistent activation of the brain’s resident immune cells (microglia) may continue for months to years after more severe injuries and lead to continuing progressive degeneration (Amor et al. 2010; Gavett et al. 2010; IOM 2009; Iwata et al. 2005).
The severity of brain injuries, described earlier in this chapter, also contributes to the heterogeneity of TBI, as the residual impact of TBI can increase as injury severity increases. The initial effects of TBI may range from mild, with a brief change in mental status or consciousness, to severe, with an extended period of unconsciousness. Ultimately, clinical severity is the result of both primary and secondary injury. Research shows a dose–response relationship between acute brain injury severity and cognitive deficits; when acute injuries are severe as measured by the GCS or PTA duration, the residual cognitive deficits are severe, may involve more cognitive domains, and are more persistent (Dikmen et al. 1995; Rohling and Demakis 2010; Schretlen and Shapiro 2003). Prospective, longitudinal studies of mild TBI have shown that by 3 months after injury, performance on cognitive tests generally does not differ from uninjured control subjects or patients who sustained mild orthopedic injury (Dikmen et al. 1995; Levin et al. 1987). Although some studies have reported more persistent cognitive deficits in a subgroup of patients with mild TBI (Kraus et al. 2007; Niogi and Mukherjee 2010), the literature is unclear about what percent of prospective patients may fall into this category.
TBI can occur as part of a polytraumatic event, meaning that other organs or body parts are injured in addition to the brain. In recognition of the multifaceted nature of physical and psychological trauma exposure to members of the military and veterans, the Department of Defense (DoD) and the U.S. Department of Veterans Affairs (VA) health care systems frequently use the term polytrauma to refer to the combination of extreme physical injuries affecting two or more organ systems, which may include emotional trauma. Polytrauma means concurrent injuries to the brain and other organ systems resulting in physical, cognitive, and psychosocial impairments (Lew et al. 2007; Sayer et al. 2009), which may complicate treatment. Concomitant injury to body regions other than the head occurs in both military and civilian trauma patients. In service members, polytrauma may result in loss of limbs and burns, complications that are less common in civilians with TBI. However, civilians with mild TBI complicated by multiple trauma have shown more frequent disability than those recovering from isolated, mild TBI (Stulemeijer et al. 2008).
In certain instances, a head injury may be followed by additional impacts to the head. Sometimes these injuries go unnoticed or unreported, as is often the case with mild TBI. Risk for repeated TBI is generally more common among military populations due to war zone characteristics, such as frequent exposure to blasts. For civilians, exposure to multiple TBIs may occur in contact sports or among those in active war zones alongside the military. Apart from developing posttraumatic dementia, the effects of sustaining more than one mild TBI on rehabilitation are unclear.
Reports of athletes sustaining repeated mild TBIs occurring over an extended period of time (i.e., months or years) have suggested that the effects are cumulative, as reflected by neurological and cognitive deficits (Guskiewicz et al. 2005; Iverson et al. 2004). It is unknown how often service members are exposed to these impacts, and blast injuries may be unreported or undetected. When reported, duration of unconsciousness is often unknown or unrecorded (Ross et al. 1994; Thatcher et al. 2001). However, studies based on self-report questionnaires and interview data obtained from service members and veterans of Iraq and Afghanistan have documented a subgroup with repeated exposure to blasts that caused alteration of consciousness (Terrio et al. 2009). Despite a dearth of prospective data, research has suggested that the effects of these repeated blast-related injuries may be cumulative (Guskiewicz et al. 2005; Laurer et al. 2001).
Although age is fixed at time of injury, it is an important factor to consider when describing the heterogeneity of TBI. Age significantly impacts outcome from TBI and is one of the strongest predictors of mortality and functional outcome (Luukinen et al. 1999; Mosenthal et al. 2002; Murray et al. 2007). Self-reported symptoms in the months after mild, blast-related TBI have been worse in younger than older service members (Hoge et al. 2008; Terrio et al. 2009). However, older TBI patients are more likely to experience a delayed neurologic decline several months after injury, which can complicate prognosis and treatment management. After age 65, and in some studies as early as age 40, morbidity and mortality after TBI increased markedly (Mosenthal et al. 2004). This finding applies especially to severe TBI in adults, where mortality rises sharply in people 40 years or older. Furthermore, as people with TBI age, they are more likely to experience cognitive decline earlier or at faster rates than individuals without TBI. Prior TBI is associated with a significantly greater incidence of dementia or Alzheimer’s disease, as established from large cohort studies from World War II, the Korean War, and the Vietnam War (Loane et al. 2009). However, the potential moderating effect of age on response to CRT is not currently known or documented.
The way gender contributes to heterogeneity of TBI varies depending upon the severity of the injury and the outcome of interest. Evidence concerning gender differences in outcome is mostly limited to sports-related concussion research, which shows that young females report more symptoms following injury (Cantu and Gean, 2010; Dikmen et al. 2010; Lovell et al. 2003). In the sports-related concussion literature, females are shown as possibly susceptible to increased risk of concussion in most sports (Colvin et al. 2009; Comstock et al. 2006; Gessel et al. 2007). In sports played by both men and women, females sustained a higher rate of mild TBI than males (Comstock et al. 2006; Gessel et al. 2007), and females were associated with worse physical and cognitive symptoms and delayed recovery following mild TBI (Broshek et al. 2005; Colvin et al. 2009; Covassin et al. 2007; Dikmen et al. 2010). Furthermore, in a large sample of junior high, high school, and collegiate soccer athletes, females had longer recovery time than males (Colvin et al. 2009). These results may be due in part to differences between genders in biomechanical forces of injury or symptom reporting. However, with increased severity of injury, evidence supports both a positive and negative effect of female gender on reducing risk of
mortality following TBI (Berry et al. 2009; Davis et al. 2006; Farace and Alves, 2000; Morrison et al. 2004; Ottochian et al. 2009).
Cognitive reserve is a construct that has been invoked to explain inter-individual variability in the response to brain injury. Higher preinjury cognitive reserve has been linked to a higher level of intellectual functioning on follow-up examinations. Operational definitions of cognitive reserve have generally used preinjury intellectual level, for which data has been available in the military. For civilians, an index based on demographic features including education history has been used; more than 11 years of education was associated with an improved outcome (Stulemeijer et al. 2008). This concept was initially proposed to explain individual differences in intellectual outcome of penetrating brain wounds sustained in combat by Korean War veterans (Weinstein and Teuber 1957). More recently, Grafman et al. (1988) extended the concept of cognitive reserve to describe long-term intellectual outcome after penetrating brain wounds in Vietnam War veterans. In both studies, higher preinjury intelligence was predictive of long-term intellectual outcome. Cognitive reserve may explain different responses to posttraumatic cognitive function, and may contribute significantly to post-traumatic outcomes and response to treatment. Higher cognitive reserve may be considered a form of resilience to neuropathological damage. A study by Jeon et al. (2008) explored premorbid demographic factors (e.g., age, sex, marriage status, educational status, occupation, residence, and premorbid intelligence) and concluded that higher levels of education, intelligence or higher IQ scores, and younger age were all prognostic indicators of recovery of memory function.
Another factor contributing to the heterogeneity of TBI is human genetic variation. At present, little is known about the role of genetic variation in brain injury or rehabilitation. However, as with many other disorders, genes are likely to emerge as an important focus in the near future and link to potential therapeutic interventions. Currently, many genetic components of the response to neurotrauma are under investigation for impact on functional outcomes. Research has shown that variation in the gene ApoE (Apolipoprotein E) can modulate the extent of brain injury (Teasdale et al. 1997). However, the nature of the effect has not been consistent (Crawford et al. 2002; Friedman et al. 1999; Millar et al. 2003). In addition, genetic polymorphisms in the p53 gene have been shown to affect TBI recovery course (Dumont et al. 2003).
Other Factors Affecting Recovery
Many chronic conditions—both clinical and premorbid demographic factors—affect outcome after TBI and therefore contribute to its heterogeneity (Jeon et al. 2008). Chapter 3 includes a more complete discussion of these other factors affecting TBI outcome, including pre- and comorbid conditions such as substance abuse or depression and posttraumatic stress disorder. In addition, the individual’s social environment context, such as family or caregiver support systems, significantly influences the effectives of treatment. Social environmental context is also discussed in Chapter 3.
Choosing outcomes to measure or monitor postinjury change is critically important in making decisions about rehabilitation for patients as well as determining the efficacy of the rehabilitation program implemented. Furthermore, prediction of outcomes is also complicated by the uniqueness of the injury as discussed throughout the chapter. While many psychometric measures of outcome are used to evaluate and report on therapeutic interventions effects, more recent rehabilitation research has focused on functional outcome measures as more global indicators of patients coping or recovering from the disability.
The most frequent cognitive sequelae of TBI are impairment of episodic memory, slowed cognitive processing speed, and impaired executive functions (i.e., the ability to switch between tasks, plan, and set and monitor goals). These findings are generally transient and relatively subtle after a single, mild TBI without complications, whereas marked persistent deficits are common after more severe TBI. Although the pattern of cognitive deficits could differ in blast-related TBI, the evidence to date indicates that the long-term effects of these injuries are similar regardless of cause and related to injury severity (Belanger et al. 2009). Rehabilitation programs must address the complexity of the cognitive deficit affecting functional capacity to be effective.
Historically, the Glasgow Outcome Scale (de Guise et al. 2008) is a common measure, which uses a five-point scale to classify outcome as death, persistent vegetative state, severe disability, moderate disability, or good recovery (Jennett et al. 1976). This was one of the first scales developed to examine outcomes and has been used widely in TBI outcome research; however, because of its broad categories that are insensitive to change and difficulties with reliability, its research application is limited. From this scale the Extended Glasgow Outcome Scale (GOS-E) was developed to address the limitations of the original GOS, measuring global functioning as a combination of neurologic functioning and gross cognitive function (Wilson et al. 1998).
Other outcome scales that are more sensitive and specific measures of functional recovery than the GOS have been proposed, including the Disability Rating Scale (DRS), Rancho Los Amigos Levels of Cognitive Function Scale (LCFS), and Functional Independence Measure (FIM) (Zafonte et al. 1996). The FIM is a widely used 18-item ordinal scale, scored on the basis of how much assistance is required for the individual to carry out activities of daily living (ADLs) (i.e., feeding, bathing, grooming, and dressing), which therefore attempts to measure the level of a patient’s disability and indicate the burden of caring for them. The FIM is often used with the Functional Assessment Measure (FAM), a 12-point scale that incorporates cognitive and psychosocial issues (Hall et al. 1993). In general these scales are more aptly suited for acute inpatient settings (Sohlberg and Mateer 2001). Many other psychometric tests are available to assess various cognitive functions (i.e., Attention Rating Scale [Ponsford and Kinsella 1991], Wechsler Memory Scale III [Wechler 1997], Wisconsin Card Sorting [Heton 1981]). However, often these measures are only indicators of what an individual can do at a particular time in a particular context (Sohlberg and Mateer 2001). Although patients may indicate improvement in by these outcome measures during or immediately posttreatment, they may fail to implement strategies learned in therapy, to home and work environments and therefore, true efficacy of therapy may not be fully captured.
Many patients, families and their caregivers are likely more interested in outcomes that generalize to real world patient functioning. These outcome measures may include those that capture patient-centered outcomes indicative of how treatment effects in the real world can be maintained or have meaning for patient (functional status and quality of life). These functional assessment measures, such as self-report or caregiver reporting of ADL functioning, can be a more useful gauge of the patient recovery trajectory. Other measures that may be more pertinent for personalized treatments involving cognitive rehabilitation therapy may include Goal Attainment Scaling (GAS) (Malec 1999, Malec et al. 1991), because it involves patients identifying general goals and articulating specific unique goals to their situation. Community participation measures including return to work, access to work, and community integration and participation measures are also important in assessing real-world functional outcomes. However, in its review of the evidence the committee focused not only on an immediate treatment benefit, but also on whether a benefit to everyday life and functional status via patient-centered outcomes, or maintenance of outcomes.
Selection of outcome measures for rehabilitation, specifically CRT, should be guided by the need to generalize treatment effects across situations and over time, while choosing measures that do not overlap with
the training tasks. Consequently, outcome measures should include cognitive function in everyday activities, and the overall study design should consider maintenance of posttreatment changes over time. Furthermore, many diagnostic tools are available to determine location of damage and lesions within the brain and to aid in determining treatment approach and options and to act as biomarkers in predicting and monitoring outcomes. These imaging techniques noninvasively monitor brain function, helping to provide information on the disease etiology and can aid in making decisions about patient recovery as well as monitor responsiveness to interventions. MRI (magnetic resonance imaging) technologies allow for the monitoring of blood flow in the brain and provide detailed images of brain anatomy to identify brain pathology. A modification of the original MRI, fMRI (functional MRI) is a relatively noninvasive monitoring and localizing of functional changes in the brain and changes in functioning following TBI. Other diagnostics include electroencephalography (EEG), which measures electrical activity from ion current within the neurons of the brain. It is generally a nonspecific indicator of general cerebral function. Positron emission tomography (PET) provides computer-generated images of blood flow, brain metabolism, and chemical processes generated from gamma rays emitted indirectly by a positron-emitting radionuclide tracer, which can be monitored while a patient is engaged in various activities. Transcranial magnetic stimulation (TMS) uses electromagnetic stimulation to activate specific or general parts of the brain with minimal discomfort, allowing study of the functioning and interconnections of the brain (Wagner et al. 2007).
These imaging technologies assist with the location of the injury and monitoring of brain function, but injury characteristic association with a performance on a functional task or with specific cognitive deficits has not been well established. However, recently, Diffusion Tensor Imaging (DTI), a method of assessing axonal integrity and white matter integrity, has shown promise as a predictor of some cognitive deficits (Kinnunen et al. 2011). White matter is one of the two components of the central nervous system and consists mostly of myelinated axons that connect regions of grey matter (the locations of nerve cell bodies) of the brain to each other, and carry nerve impulses between neurons, thus white matter acts as the tracts to connect brain functionality. Kinnunen and colleagues (2011) demonstrated the relationship between white matter abnormalities and cognitive function in two domains commonly affected by TBI, memory and executive function (Kinnunen et al. 2011). These imaging and biomarkers may have utility in determining responsiveness to behavioral/rehabilitative interventions and or medications and be useful in helping to define target populations.
In general, TBI is complex, and a multitude of factors may influence treatment approaches and course of recovery. The nature of TBI complicates the process of planning, delivering, and evaluating therapeutic interventions such as CRT. This chapter serves as background for the remainder of the report, including understanding what CRT is and the lack of definitive evidence regarding effective treatment for TBI.
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