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2
Traumatic Brain Injury
The multifaceted characteristics of traumatic brain injury (TBI) com-
plicate 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 re-
covery (Maas et al. 2008). These combined factors may determine the type
and effectiveness of the rehabilitation therapy. In this chapter, the patho-
physiology 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, sec-
ondary 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 complicat-
ing factors such as hemorrhage, hypoxia, reduced blood flow, or metabolic
37
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38 COGNITIVE REHABILITATION THERAPY FOR TBI
alterations (Jeremitsky et al. 2003; Saatman et al. 2008). These early, acute
events are highly relevant to long-term outcomes, as they can critically af-
fect an individual’s degree of disability and need for rehabilitation. The fol-
lowing 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 irrepara-
bly 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.
CLASSIFICATION SCHEMES
Head injuries have historically been classified using various clinical in-
dexes that include pathoanatomical features, severity of injury, or the physi-
cal 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.
Pathoanatomical Classification
Sometimes known as the “where and what” of TBI classification,
pathoanatomical classification describes the location and the pathological
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39
TRAUMATIC BRAIN INJURY
features (i.e., pathoanatomy) of tissue damage induced by the injury. Patho-
anatomical 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). Patho-
anatomical 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). Imag-
ing helps with location of injury, which can be useful in understanding lo-
calization of deficits (e.g., frontal lobe injuries are associated with problems
with attention, initiating activity) (Kringelbach and Rolls 2004).
Severity Scales
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 of-
ten 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
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40 COGNITIVE REHABILITATION THERAPY FOR TBI
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 behav-
ior (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 intuba-
tion 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
TABLE 2-1 Classification of Mild, Moderate, and Severe Traumatic
Brain Injury
Severity of Injury/Measure Mild Moderate Severe
Glasgow Coma Scale 13 to 15 9 to 12 3 to 8
Loss of Consciousness 30 minutes > 24 hours
< 24 hours to 24 hours
≥ 7 days
Posttraumatic Amnesia 24 hours
< 7 days
≤ 24 hours
Altered Consciousness > 24 hours > 24 hours
SOURCES: Helmick et al. 2007; Kay et al. 1993.
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41
TRAUMATIC BRAIN INJURY
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 imme-
diately 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 ini-
tial injury severity, as described with the GCS, though there can be con-
siderable 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 symp-
toms 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 great-
est 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 approxi-
mately 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.
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42 COGNITIVE REHABILITATION THERAPY FOR TBI
HETEROGENEITY
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 includ-
ing 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 decel-
eration 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 preced-
ing 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 fol-
lowing 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
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TRAUMATIC BRAIN INJURY
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 character-
ized 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 fea-
tures 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 signifi-
cantly 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, re-
sulting in either diffuse or focal injury. When not accompanied by penetrat-
ing 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
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44 COGNITIVE REHABILITATION THERAPY FOR TBI
[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 in-
juries, 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 atmo-
spheric 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 machin-
ery. 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; pend-
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TRAUMATIC BRAIN INJURY
ing development of further research, the true impact of these injuries on
short- and long-term outcomes for survivors are unknown.
Pathobiology
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 physiologi-
cal changes related to biochemical alterations at the molecular and cellular
level. In addition, secondary insults, such as hypoxia, hypotension, hypercar-
bia, 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 degenera-
tion (Amor et al. 2010; Gavett et al. 2010; IOM 2009; Iwata et al. 2005).
Severity Continuum
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 sever-
ity is the result of both primary and secondary injury. Research shows a
dose–response relationship between acute brain injury severity and cogni-
tive 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.
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46 COGNITIVE REHABILITATION THERAPY FOR TBI
Polytrauma
TBI can occur as part of a polytraumatic event, meaning that other or-
gans or body parts are injured in addition to the brain. In recognition of the
multifaceted nature of physical and psychological trauma exposure to mem-
bers 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. Concomi-
tant 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).
Multiple TBIs
In certain instances, a head injury may be followed by additional im-
pacts 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 altera-
tion 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).
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TRAUMATIC BRAIN INJURY
Age
Although age is fixed at time of injury, it is an important factor to con-
sider 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). How-
ever, the potential moderating effect of age on response to CRT is not cur-
rently known or documented.
Gender
The way gender contributes to heterogeneity of TBI varies depending
upon the severity of the injury and the outcome of interest. Evidence con-
cerning gender differences in outcome is mostly limited to sports-related
concussion research, which shows that young females report more symp-
toms 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 associ-
ated 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
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48 COGNITIVE REHABILITATION THERAPY FOR TBI
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
Cognitive reserve is a construct that has been invoked to explain inter-
individual variability in the response to brain injury. Higher preinjury cog-
nitive 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 avail-
able 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 intellec-
tual 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 intel-
lectual 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, intel-
ligence or higher IQ scores, and younger age were all prognostic indicators
of recovery of memory function.
Genetic Variation
Another factor contributing to the heterogeneity of TBI is human ge-
netic 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).
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TRAUMATIC BRAIN INJURY
Other Factors Affecting Recovery
Many chronic conditions—both clinical and premorbid demographic
factors—affect outcome after TBI and therefore contribute to its hetero-
geneity (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.
MEASURES OF OUTCOME
Choosing outcomes to measure or monitor postinjury change is criti-
cally 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 psychomet-
ric 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 de-
veloped 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 de-
veloped 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).
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50 COGNITIVE REHABILITATION THERAPY FOR TBI
Other outcome scales that are more sensitive and specific measures of
functional recovery than the GOS have been proposed, including the Dis-
ability Rating Scale (DRS), Rancho Los Amigos Levels of Cognitive Func-
tion 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 dis-
ability and indicate the burden of caring for them. The FIM is often used
with the Functional Assessment Measure (FAM), a 12-point scale that in-
corporates 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 vari-
ous 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 out-
come 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 situ-
ations and over time, while choosing measures that do not overlap with
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51
TRAUMATIC BRAIN INJURY
the training tasks. Consequently, outcome measures should include cogni-
tive 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 ner-
vous 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.
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52 COGNITIVE REHABILITATION THERAPY FOR TBI
CONCLUSION
In general, TBI is complex, and a multitude of factors may influence
treatment approaches and course of recovery. The nature of TBI compli-
cates the process of planning, delivering, and evaluating therapeutic inter-
ventions such as CRT. This chapter serves as background for the remainder
of the report, including understanding what CRT is and the lack of defini-
tive evidence regarding effective treatment for TBI.
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