Handbook of Clinical Neurology, Vol. 128 (3rd series) Traumatic Brain Injury, Part II J. Grafman and A.M. Salazar, Editors © 2015 Elsevier B.V. All rights reserved
Chapter 37
Traumatic brain injury and cognition IRENE CRISTOFORI1 AND HARVEY S. LEVIN2* Cognitive Neuroscience Laboratory, Rehabilitation Institute of Chicago, Chicago, IL, USA
1 2
Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, USA
INTRODUCTION Traumatic brain injury (TBI) is defined as an alteration in brain function or other evidence of brain pathology caused by external forces (Menon et al., 2010). These external forces can induce vascular and axonal damages, edema, and neuronal cell death (Zetterberg et al., 2013). TBI is the principal cause of death and disability worldwide; in the US alone, 1.7 million new TBIs occur each year among Americans under the age of 35 (Faul et al., 2010a) (see Ch. 1 for a full discussion on TBI epidemiology). Damages to the brain result in a cascade of pathologic events including neural dysfunctions, and disruption of neural networks. These pathologic events alter the brain anatomy and physiology. Therefore, brain injuries often result in lifelong impairments, and over 3 million Americans are living with chronic disabilities because of TBI (Zaloshnja et al., 2008). Deficits or impairments refer to cognitive or social dysfunctions related to specific brain lesions, and may recover over time due to brain plasticity. Disability refers to everyday life difficulties because of a specific impairment (e.g., cognitive) or of a combination of impairments (e.g., cognitive and motor). Deficits or impairments that persist over a long period may predict disabilities that affect everyday life. For example, consistent impairments in attention may predict specific difficulties with focus during daily tasks or with the ability to maintain conversations. Most brain injuries involve damage to the prefrontal cortex (PFC) and temporal lobe that have been linked to cognitive and social functioning. Cognitive deficits often result in long-lasting disability over time, depending on lesion extent and location, in addition to recovery mechanisms after the injury, such as brain plasticity. These deficits involve a variety of impairments such
as difficulties in general intelligence, memory, executive functions, and attention, and patients are often unaware of their deficits. The effects of these deficits vary in terms of their severity and chronicity, and may result in disabilities affecting work, school, family relationships, and community involvement. Brain injuries are also often associated with the development of comorbidities including depression (Hart et al., 2012), post-traumatic stress disorder (Hoffman et al., 2012), and epilepsy (Annegers and Coan, 2000). In this chapter, the first sections will define TBI based on the severity of the injury, physical mechanism causing the injury, and chronicity level. Subsequent sections will outline the major cognitive deficits observed in TBI patients, including impairment in general intelligence, memory, executive functions, attention, and awareness. These cognitive deficits will be discussed in terms of their varying levels of severity (mild, moderate, and severe) and typology (closed, penetrating, blast, and concussion). Particular attention will also be given to differences between pediatric and adult TBI. A further section will detail the guidelines of the Common Data Elements (CDEs) working group in order to develop data standards for improving clinical research on TBI. The following section will explore the extent to which new neuroimaging techniques can provide indications for diagnosis and treatment. Finally, current techniques in cognitive rehabilitation will be discussed, as well as the potential for genetics to provide important information about recovery.
SPECTRUM OF TRAUMATIC BRAIN INJURY SEVERITY An efficient and reliable classification of TBI severity can be extremely helpful in evaluating and providing
*Correspondence to: Harvey S. Levin, Ph.D., Cognitive Neuroscience Laboratory, 1709 Dryden Road, Suite #725, Houston, TX 77030, USA. Tel: +1-713-798-7566, Fax: +1-713-798-6898, E-mail: [email protected]
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I. CRISTOFORI AND H.S. LEVIN
optimal therapeutic interventions (see Ch. 2 for a detailed classification of TBI). The American Congress of Rehabilitation Medicine (ACRM) divides TBI severity into three broad categories: mild, moderate, and severe (Kay et al., 1993). Severity classification is based on acute effects of the injury, which involve loss of consciousness. The patient’s level of consciousness is assessed after resuscitation (if performed) following the TBI, using the Glasgow Coma Scale (GCS) (Teasdale and Jennett, 1974). The GCS is a 15 point neurologic scale assessing eye, motor, and verbal responses. The GCS has a high interobserver reliability and good prognostic capability (Narayan et al., 2002). This measure, however, is not optimal for infants, young children, and patients with preinjury neurologic deficits, and is not sensitive in discriminating mild TBI (Saatman et al., 2008). Other classifications of severity include the duration of post-traumatic amnesia (PTA) (Levin et al., 1979) and loss of consciousness (LOC) (Ptak et al., 1998). PTA refers to a state of confusion which occurs after the TBI and whose duration is variable. During this period, the patient is disoriented and shows difficulty forming new short-term memories (Zuccarelli, 2000). PTA is generally assessed using the Galveston Orientation and Amnesia Test (Levin et al., 1979), which measures the spatial and temporal orientation of events before and after the injury. The duration of LOC is assessed during the acute phase after TBI. This measure has been historically used as a marker to establish outcomes after TBI. In fact, several studies have reported significant correlations between TBI severity and LOC duration (Cifu et al., 1997; Sherer et al., 2002; Dikmen et al., 2003; Temkin et al., 2003). However, evidence is mixed, as at least one recent study did not provide evidence of a relationship between LOC and neuropsychological outcomes, despite use of a large sample of patients (Lovell et al., 1999). In general, it appears that measures obtained later in the course of TBI recovery, such as PTA, are better predictors of long-term outcomes.
The severity indices described above allow categorizing the TBI as mild, moderate, or severe. The Table 37.1 provides a summary of the TBI severity spectrum. It is important to acknowledge that there are different definitions of mild TBI, including some that do not require normal structural neuroimaging. Indeed, the World Health Organization (WHO) Collaborating Centre Task Force reported that abnormalities are present in 5% and 30% of computed tomography (CT) scans on mild TBI patients with a GCS score of 15 and 13, respectively (see Borg et al., 2004, for a review). The approximate distribution of severity is 80%, 10%, and 10% for mild, moderate, and severe TBI, respectively (Bruns and Hauser, 2003). However, a recent large-scale study conducted by Feigin and colleagues (2013) suggested that mild TBIs have greater incidence than previously reported. In this study, the authors found that mild TBIs corresponded to 95% of the total sample (Feigin et al., 2013). The fact that frequency of mild TBIs has been underestimated might be due to the lack of evidence supporting structural injury in the standard neuroimaging examinations performed after mild TBIs. Despite this absence of clear structural damage, neurochemical cascade processes – not detectable by current neuroimaging methods – are sufficient to produce neural dysfunction. On the other hand, in moderate and severe TBI, the force of the trauma determines the disruption of axons and gray matter detectable on the neuroimaging examinations. Studies comparing outcomes after mild, moderate, and severe TBI have found that severity level plays a role in determining the type and intensity of subsequent cognitive impairment (Cifu et al., 1997; Sherer et al., 2002; Dikmen et al., 2009). Mild and moderate TBI are associated with specific cognitive impairments (Ruff et al., 1986; Vanderploeg et al., 2005), whereas severe TBI is associated with more generalized impairment in several cognitive domains (Ruff et al., 1986; Bate et al., 2001a; Incoccia et al., 2004). Furthermore, the intensity of these cognitive deficits increases as a function of injury
Table 37.1 Classification of traumatic brain injury severity Mild
Moderate
Severe
Glasgow Coma Scale Loss of consciousness
13–15 24 hours
Post-traumatic amnesia
30 minutes 24 hours 24 hours Normal or abnormal
7 days >24 hours Normal or abnormal
TRAUMATIC BRAIN INJURY AND COGNITION severity, with severe TBI causing greater and longer lasting cognitive deficits than mild and moderate TBI (Levin et al., 1987; Satz et al., 1998; Rapoport et al., 2002; Jamora et al., 2012). It is important to note, however, that although categorizing TBI severity as mild, moderate, and severe may help clinicians in first assessing TBI patients, this categorization does not reflect the heterogeneity of pathology and impairment in individual patients. Other factors need to be taken into account when using severity categorization to predict outcome, such as patient age, extracranial injuries, and physiologic conditions.
SPECTRUM OF PHYSICAL MECHANISMS CAUSING TRAUMATIC BRAIN INJURY Another classification of TBI involves the physical mechanism causing the injury. Examples of physical mechanisms that can induce a TBI include accelerations of the head, explosions, or foreign bodies penetrating the brain. Defining TBI according to the physical mechanism that caused the brain damage can provide key information regarding expected long-term outcomes. For instance, it has been shown that head accelerations produce diffuse axonal injury (DAI) and the amount of DAI is directly correlated to the severity of the injury (duration of the coma and quality of the outcomes (Gennarelli et al., 1982)). Based on the physical mechanism causing the injury, TBI are classified as closed, penetrating, blast, and concussion. (See Ch. 4 for a full discussion on the neuropathology mechanisms linked to TBI and Ch. 5 for a review of the molecular mechanisms associated to the different types of injury.) Closed TBIs result from rapid rotations, accelerations/ decelerations, shaking of the brain within the skull, or impact to the skull itself often resulting from motor vehicle collisions. The extent of rotational acceleration of the brain determines the stretching and shearing of axons, which is generally multifocal or diffuse. “Diffuse” injuries imply extensive damage, causing the degeneration of gray and white matter and can vary in severity (mild, moderate, or severe). In closed TBIs, the duration of the LOC and PTA are indices of the severity of diffuse injury, and predict residual cognitive deficits. Penetrating TBIs are defined as focal brain lesions produced by the entrance of an external object into the cranial cavity. The profile of cognitive deficits manifested by penetrating TBIs is specific to lesion location. Unlike closed TBIs, the severity of penetrating TBIs cannot be accurately characterized based on LOC or PTA (Meyer et al., 2008). In general, severity is not measured by LOC/PTA in these injuries, which might not produce LOC or only momentary LOC (Salazar et al., 1986). In civilian populations, penetrating TBIs
581
are most often a result of projectiles or knife wounds; in military settings, the most common causes are blast-related shrapnel or missile injuries (Warden, 2006). Although penetrating injuries produce specific focal lesions, they can also cut across cortical or subcortical pathways (Povlishock and Katz, 2005). Penetrating TBIs generally lead to worse outcomes than closed TBIs. Blast TBIs are the result of wave-induced changes in atmospheric pressure caused by a blast explosion (DePalma et al., 2005). Secondary blast injury involves penetrating and blunt trauma, while tertiary blast injury occurs when the body is displaced, striking a surface. Quaternary blast injury involves other mechanisms, such as toxic inhalation, and radiation. Recently, a Veterans Affairs study found that 56% of its war-injured sample had been injured by blasts. Belanger and collaborators (2009) reported that blast and nonblast TBIs have a comparable cognitive functioning. This similarity in cognitive functioning may be due to reports that blast-related TBI involves axonal injury similar to the neuropathology reported in civilian TBI (Oppenheimer, 1968; Blumbergs et al., 1994). Concussion TBI is a relevant subcategory of brain injury; it is essentially mild TBI. Concussion TBI differs from other TBI because the trauma is sport-related. In fact, concussions are typically caused by high-impact sports including boxing, American football, ice hockey, soccer, and rugby. Concussions can derive from a direct bump, blow, or jolt to the head, but also from a fall or a blow to the body that causes the brain to move rapidly back and forth. Concussions result in the rapid development of neurologic symptoms such as headache, dizziness, and memory deficits. In adults, most concussion TBIs resolve within 1 week; however, athletes who have been exposed to repeated concussions and show hyperactivation in the impacted region (via fMRI) have shown prolonged clinical recovery (Aubry et al., 2002).
SPECTRUM OF CHRONICITY IN RELATION TO COGNITIVE FUNCTIONS In terms of chronicity, TBI can be divided in acute, subacute, and chronic TBI, according to the phase of recovery. Whereas acute TBI refers to the phase that occurs close to the time of impact, chronic TBI refers to the phase involving long-term consequences of brain injury, and subacute TBI refers to an intermediate time between acute and chronic TBI. The duration of each phase depends upon the severity of the TBI. Table 37.2 describes the different phases of recovery in mild and moderate-severe TBI. Chronicity of TBI is associated with white matter changes after injury (Kennedy et al., 2009). Because Wallerian degeneration (the process by which axons
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I. CRISTOFORI AND H.S. LEVIN
Table 37.2 Definition of recovery phase of traumatic brain injury Phases
Mild
Moderate-severe
Acute Subacute
3 months < 6 months >6 months < 12 months
Acute hospital care Inpatient rehabilitation
Chronic
Outpatient rehabilitation
degenerate after separating from the neuron’s cell body) continues after initial recovery, it is important to assess white matter changes following recovery from TBI. Recently, several studies have used diffusion tensor imaging (DTI) to document changes of white matter in chronic TBI (Mathias et al., 2004; Yuan et al., 2007). Salmond and colleagues (2006), for example, using DTI in patients with chronic TBI, found significant changes in white matter integrity at 6 months postinjury. These changes involved an extensive reduction in anisotropy (a measure of the proportion of diffusion in the direction parallel to the long axis of the white matter tract) and increase in diffusivity (a measure of the magnitude of the diffusion) (Salmond et al., 2006). Another recent study compared changes in white matter tracts and cognitive functions in adults with mild, moderate, and severe TBI at 10 years postinjury. Compared to healthy controls, patients with moderate and severe TBI showed decreases in white matter anisotropy throughout the brain (Kraus et al., 2007).
Recovery course The natural recovery process after TBI is dependent upon the level of injury severity (mild, moderate, or severe). Patients with mild TBI typically return to their preinjury cognitive level within 3–6 months postinjury (Schretlen and Shapiro, 2003; Belanger et al., 2005). Conversely, patients with moderate and severe TBI recover slowly and frequently do not return to their preinjury cognitive level (Dikmen et al., 2003). Although recovery is associated with injury severity, it is important to remember that each recovery is an individualized process that depends on many other factors, such as age, general health, preinjury cognitive functioning (Raymont et al., 2008), psychiatric comorbidities, social environment (family, friends, work), and PTA duration. The combination of these factors determines the pattern of recovery from TBI, as shown in Figure 37.1 (Faul et al., 2010b). Generally, 85–95% of persons who have suffered a mild TBI will make a complete recovery, as compared to 60% of those who have experienced a moderate
Fig. 37.1. Typical temporal course of recovery in mild, moderate, and severe traumatic brain injury (TBI).
TBI and 15–20% of those who have experienced a severe TBI. Most patients with mild TBI recover in 3 months. Recent studies showed that the majority of patients with mild TBI recovered, but between 5% and 15% retained long-lasting impairments (Faul et al., 2010b). The likelihood of developing such long-term impairments increases when neuroimaging examination reveals structural/functional damage during the acute phase of the injury. Patients with this type of damage comprise a subcategory of mild TBI termed “complicated mild TBI,” and often continue to show symptoms of cognitive impairment over 6 months following the injury (Williams et al., 1990). Patients with moderate to severe TBI often exhibit persisting disability and cognitive impairments. A recent study found that, at 1 year postinjury, 47% of hospitalized patients reported functional difficulties (Pickelsimer et al., 2006). Another study indicated that 24% of patients hospitalized for moderate-severe TBI failed to return to work 1 year after the injury (Whiteneck et al., 2004). Similarly, a study on brain injury in Vietnam veterans reported that only 56% of participants with penetrating TBI were employed at 15 years postinjury, compared with 82 % of nonphysically injured veterans (Schwab et al., 1993). In addition to cognitive and functional impairment, patients with moderate and severe TBI also show higher rates of psychopathology (e.g., depression) in comparison to matched controls (Vanderploeg et al., 2007a).
COGNITIVE SEQUELAE OF TRAUMATIC BRAIN INJURY Functional and structural brain damage cause various neuropsychological impairments, including reductions in information processing speed, memory, as well as deficits in attention and executive functioning (Hopkins et al., 2005; O’Jile et al., 2006; Benson et al.,
TRAUMATIC BRAIN INJURY AND COGNITION 583 2007; Mathias and Wheaton, 2007; Fleminger, 2008). deficits associated with closed TBI can vary according Impairments in executive functioning affect mental to the TBI classification as mild or moderate-severe, flexibility, planning, self-monitoring, and problem solvas described below. ing (Bigler, 2007). Longitudinal studies on cognitive sequelae after TBI Mild closed traumatic brain injury can provide a better understanding of the time course of In a classic study examining longitudinal outcomes in recovery (Levin et al., 1990; Novack et al., 2000). Imporpatients with mild closed TBI, Dikmen and collaborators tantly, if performance on multiple cognitive tasks is fol(1986) tested cognitive ability at both 1 month and 1 year lowed over the course of recovery, researchers can then after injury. Patients in this study had a GCS score equal identify those tasks that best predict long-term outcomes to or greater than 12, an LOC of less than 1 hour, a PTA (see Ch. 29 for a detailed discussion on factors predicting of at least 1 hour, with no clinical evidence of brain outcome after TBI). Indeed, performance on neuropsycontusion. At 1 month after the injury, patients with mild chological tests 1 year after a severe TBI has been related TBI performed worse than matched controls in tests of to neuropsychological performance during the acute attention and memory (the Seashore Rhythm Test and phase of injury (Levin et al., 1990; Novack et al., the Selective Reminding Test); however, patients did 2000). For instance, Levin and collaborators (1990) not show impairments on other cognitive tasks, such showed that neuropsychological deficits in memory as the Trail Making Test and Wechsler Memory Scale. and information processing speed could persist at 1 year At 1 year after the injury, there were no significant postinjury, whereas language and visuospatial functions differences between mild TBI patients and control had recovered by that time (Levin et al., 1990). The same participants on any cognitive task. In a similar study, study established that lower GCS scores and pupillary Dikmen and collaborators (1987) examined the relationreactivity immediately following the injury predicted ship between injury severity and memory in patients with neuropsychological task performance at 1 year postinmild to moderate closed TBI, in comparison with jury. Novack and collaborators (2000) examined a more matched controls (Dikmen et al., 1987). Memory funcdetailed time course of TBI recovery, with neuropsychotion was assessed using the Wechsler Memory Scale logical assessments administered to TBI patients at and the Selective Reminding Test at 1 and 12 months 1 month intervals, between 6 and 12 months after injury. after the head injury. On average, patients with TBI Over the course of these 6 months, TBI patients showed had lower scores than the control participants on each consistent improvements in memory skills, speed prosubscale of the Wechsler Memory Scale and the Selective cessing and language, as well as community integration Reminding Test, at 1 month following the injury. Simiand quality of their daily life activities (Novack et al., larly, at 12 months, TBI patients showed increased scores 2000). Results from these types of studies are critical on most subscales of both tests, on average. However, in predicting the cognitive, behavioral, and emotional TBI patients with prolonged impaired consciousness time course of recovery after TBI. (PTA
Chapter 37
Traumatic brain injury and cognition IRENE CRISTOFORI1 AND HARVEY S. LEVIN2* Cognitive Neuroscience Laboratory, Rehabilitation Institute of Chicago, Chicago, IL, USA
1 2
Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX, USA
INTRODUCTION Traumatic brain injury (TBI) is defined as an alteration in brain function or other evidence of brain pathology caused by external forces (Menon et al., 2010). These external forces can induce vascular and axonal damages, edema, and neuronal cell death (Zetterberg et al., 2013). TBI is the principal cause of death and disability worldwide; in the US alone, 1.7 million new TBIs occur each year among Americans under the age of 35 (Faul et al., 2010a) (see Ch. 1 for a full discussion on TBI epidemiology). Damages to the brain result in a cascade of pathologic events including neural dysfunctions, and disruption of neural networks. These pathologic events alter the brain anatomy and physiology. Therefore, brain injuries often result in lifelong impairments, and over 3 million Americans are living with chronic disabilities because of TBI (Zaloshnja et al., 2008). Deficits or impairments refer to cognitive or social dysfunctions related to specific brain lesions, and may recover over time due to brain plasticity. Disability refers to everyday life difficulties because of a specific impairment (e.g., cognitive) or of a combination of impairments (e.g., cognitive and motor). Deficits or impairments that persist over a long period may predict disabilities that affect everyday life. For example, consistent impairments in attention may predict specific difficulties with focus during daily tasks or with the ability to maintain conversations. Most brain injuries involve damage to the prefrontal cortex (PFC) and temporal lobe that have been linked to cognitive and social functioning. Cognitive deficits often result in long-lasting disability over time, depending on lesion extent and location, in addition to recovery mechanisms after the injury, such as brain plasticity. These deficits involve a variety of impairments such
as difficulties in general intelligence, memory, executive functions, and attention, and patients are often unaware of their deficits. The effects of these deficits vary in terms of their severity and chronicity, and may result in disabilities affecting work, school, family relationships, and community involvement. Brain injuries are also often associated with the development of comorbidities including depression (Hart et al., 2012), post-traumatic stress disorder (Hoffman et al., 2012), and epilepsy (Annegers and Coan, 2000). In this chapter, the first sections will define TBI based on the severity of the injury, physical mechanism causing the injury, and chronicity level. Subsequent sections will outline the major cognitive deficits observed in TBI patients, including impairment in general intelligence, memory, executive functions, attention, and awareness. These cognitive deficits will be discussed in terms of their varying levels of severity (mild, moderate, and severe) and typology (closed, penetrating, blast, and concussion). Particular attention will also be given to differences between pediatric and adult TBI. A further section will detail the guidelines of the Common Data Elements (CDEs) working group in order to develop data standards for improving clinical research on TBI. The following section will explore the extent to which new neuroimaging techniques can provide indications for diagnosis and treatment. Finally, current techniques in cognitive rehabilitation will be discussed, as well as the potential for genetics to provide important information about recovery.
SPECTRUM OF TRAUMATIC BRAIN INJURY SEVERITY An efficient and reliable classification of TBI severity can be extremely helpful in evaluating and providing
*Correspondence to: Harvey S. Levin, Ph.D., Cognitive Neuroscience Laboratory, 1709 Dryden Road, Suite #725, Houston, TX 77030, USA. Tel: +1-713-798-7566, Fax: +1-713-798-6898, E-mail: [email protected]
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I. CRISTOFORI AND H.S. LEVIN
optimal therapeutic interventions (see Ch. 2 for a detailed classification of TBI). The American Congress of Rehabilitation Medicine (ACRM) divides TBI severity into three broad categories: mild, moderate, and severe (Kay et al., 1993). Severity classification is based on acute effects of the injury, which involve loss of consciousness. The patient’s level of consciousness is assessed after resuscitation (if performed) following the TBI, using the Glasgow Coma Scale (GCS) (Teasdale and Jennett, 1974). The GCS is a 15 point neurologic scale assessing eye, motor, and verbal responses. The GCS has a high interobserver reliability and good prognostic capability (Narayan et al., 2002). This measure, however, is not optimal for infants, young children, and patients with preinjury neurologic deficits, and is not sensitive in discriminating mild TBI (Saatman et al., 2008). Other classifications of severity include the duration of post-traumatic amnesia (PTA) (Levin et al., 1979) and loss of consciousness (LOC) (Ptak et al., 1998). PTA refers to a state of confusion which occurs after the TBI and whose duration is variable. During this period, the patient is disoriented and shows difficulty forming new short-term memories (Zuccarelli, 2000). PTA is generally assessed using the Galveston Orientation and Amnesia Test (Levin et al., 1979), which measures the spatial and temporal orientation of events before and after the injury. The duration of LOC is assessed during the acute phase after TBI. This measure has been historically used as a marker to establish outcomes after TBI. In fact, several studies have reported significant correlations between TBI severity and LOC duration (Cifu et al., 1997; Sherer et al., 2002; Dikmen et al., 2003; Temkin et al., 2003). However, evidence is mixed, as at least one recent study did not provide evidence of a relationship between LOC and neuropsychological outcomes, despite use of a large sample of patients (Lovell et al., 1999). In general, it appears that measures obtained later in the course of TBI recovery, such as PTA, are better predictors of long-term outcomes.
The severity indices described above allow categorizing the TBI as mild, moderate, or severe. The Table 37.1 provides a summary of the TBI severity spectrum. It is important to acknowledge that there are different definitions of mild TBI, including some that do not require normal structural neuroimaging. Indeed, the World Health Organization (WHO) Collaborating Centre Task Force reported that abnormalities are present in 5% and 30% of computed tomography (CT) scans on mild TBI patients with a GCS score of 15 and 13, respectively (see Borg et al., 2004, for a review). The approximate distribution of severity is 80%, 10%, and 10% for mild, moderate, and severe TBI, respectively (Bruns and Hauser, 2003). However, a recent large-scale study conducted by Feigin and colleagues (2013) suggested that mild TBIs have greater incidence than previously reported. In this study, the authors found that mild TBIs corresponded to 95% of the total sample (Feigin et al., 2013). The fact that frequency of mild TBIs has been underestimated might be due to the lack of evidence supporting structural injury in the standard neuroimaging examinations performed after mild TBIs. Despite this absence of clear structural damage, neurochemical cascade processes – not detectable by current neuroimaging methods – are sufficient to produce neural dysfunction. On the other hand, in moderate and severe TBI, the force of the trauma determines the disruption of axons and gray matter detectable on the neuroimaging examinations. Studies comparing outcomes after mild, moderate, and severe TBI have found that severity level plays a role in determining the type and intensity of subsequent cognitive impairment (Cifu et al., 1997; Sherer et al., 2002; Dikmen et al., 2009). Mild and moderate TBI are associated with specific cognitive impairments (Ruff et al., 1986; Vanderploeg et al., 2005), whereas severe TBI is associated with more generalized impairment in several cognitive domains (Ruff et al., 1986; Bate et al., 2001a; Incoccia et al., 2004). Furthermore, the intensity of these cognitive deficits increases as a function of injury
Table 37.1 Classification of traumatic brain injury severity Mild
Moderate
Severe
Glasgow Coma Scale Loss of consciousness
13–15 24 hours
Post-traumatic amnesia
30 minutes 24 hours 24 hours Normal or abnormal
7 days >24 hours Normal or abnormal
TRAUMATIC BRAIN INJURY AND COGNITION severity, with severe TBI causing greater and longer lasting cognitive deficits than mild and moderate TBI (Levin et al., 1987; Satz et al., 1998; Rapoport et al., 2002; Jamora et al., 2012). It is important to note, however, that although categorizing TBI severity as mild, moderate, and severe may help clinicians in first assessing TBI patients, this categorization does not reflect the heterogeneity of pathology and impairment in individual patients. Other factors need to be taken into account when using severity categorization to predict outcome, such as patient age, extracranial injuries, and physiologic conditions.
SPECTRUM OF PHYSICAL MECHANISMS CAUSING TRAUMATIC BRAIN INJURY Another classification of TBI involves the physical mechanism causing the injury. Examples of physical mechanisms that can induce a TBI include accelerations of the head, explosions, or foreign bodies penetrating the brain. Defining TBI according to the physical mechanism that caused the brain damage can provide key information regarding expected long-term outcomes. For instance, it has been shown that head accelerations produce diffuse axonal injury (DAI) and the amount of DAI is directly correlated to the severity of the injury (duration of the coma and quality of the outcomes (Gennarelli et al., 1982)). Based on the physical mechanism causing the injury, TBI are classified as closed, penetrating, blast, and concussion. (See Ch. 4 for a full discussion on the neuropathology mechanisms linked to TBI and Ch. 5 for a review of the molecular mechanisms associated to the different types of injury.) Closed TBIs result from rapid rotations, accelerations/ decelerations, shaking of the brain within the skull, or impact to the skull itself often resulting from motor vehicle collisions. The extent of rotational acceleration of the brain determines the stretching and shearing of axons, which is generally multifocal or diffuse. “Diffuse” injuries imply extensive damage, causing the degeneration of gray and white matter and can vary in severity (mild, moderate, or severe). In closed TBIs, the duration of the LOC and PTA are indices of the severity of diffuse injury, and predict residual cognitive deficits. Penetrating TBIs are defined as focal brain lesions produced by the entrance of an external object into the cranial cavity. The profile of cognitive deficits manifested by penetrating TBIs is specific to lesion location. Unlike closed TBIs, the severity of penetrating TBIs cannot be accurately characterized based on LOC or PTA (Meyer et al., 2008). In general, severity is not measured by LOC/PTA in these injuries, which might not produce LOC or only momentary LOC (Salazar et al., 1986). In civilian populations, penetrating TBIs
581
are most often a result of projectiles or knife wounds; in military settings, the most common causes are blast-related shrapnel or missile injuries (Warden, 2006). Although penetrating injuries produce specific focal lesions, they can also cut across cortical or subcortical pathways (Povlishock and Katz, 2005). Penetrating TBIs generally lead to worse outcomes than closed TBIs. Blast TBIs are the result of wave-induced changes in atmospheric pressure caused by a blast explosion (DePalma et al., 2005). Secondary blast injury involves penetrating and blunt trauma, while tertiary blast injury occurs when the body is displaced, striking a surface. Quaternary blast injury involves other mechanisms, such as toxic inhalation, and radiation. Recently, a Veterans Affairs study found that 56% of its war-injured sample had been injured by blasts. Belanger and collaborators (2009) reported that blast and nonblast TBIs have a comparable cognitive functioning. This similarity in cognitive functioning may be due to reports that blast-related TBI involves axonal injury similar to the neuropathology reported in civilian TBI (Oppenheimer, 1968; Blumbergs et al., 1994). Concussion TBI is a relevant subcategory of brain injury; it is essentially mild TBI. Concussion TBI differs from other TBI because the trauma is sport-related. In fact, concussions are typically caused by high-impact sports including boxing, American football, ice hockey, soccer, and rugby. Concussions can derive from a direct bump, blow, or jolt to the head, but also from a fall or a blow to the body that causes the brain to move rapidly back and forth. Concussions result in the rapid development of neurologic symptoms such as headache, dizziness, and memory deficits. In adults, most concussion TBIs resolve within 1 week; however, athletes who have been exposed to repeated concussions and show hyperactivation in the impacted region (via fMRI) have shown prolonged clinical recovery (Aubry et al., 2002).
SPECTRUM OF CHRONICITY IN RELATION TO COGNITIVE FUNCTIONS In terms of chronicity, TBI can be divided in acute, subacute, and chronic TBI, according to the phase of recovery. Whereas acute TBI refers to the phase that occurs close to the time of impact, chronic TBI refers to the phase involving long-term consequences of brain injury, and subacute TBI refers to an intermediate time between acute and chronic TBI. The duration of each phase depends upon the severity of the TBI. Table 37.2 describes the different phases of recovery in mild and moderate-severe TBI. Chronicity of TBI is associated with white matter changes after injury (Kennedy et al., 2009). Because Wallerian degeneration (the process by which axons
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I. CRISTOFORI AND H.S. LEVIN
Table 37.2 Definition of recovery phase of traumatic brain injury Phases
Mild
Moderate-severe
Acute Subacute
3 months < 6 months >6 months < 12 months
Acute hospital care Inpatient rehabilitation
Chronic
Outpatient rehabilitation
degenerate after separating from the neuron’s cell body) continues after initial recovery, it is important to assess white matter changes following recovery from TBI. Recently, several studies have used diffusion tensor imaging (DTI) to document changes of white matter in chronic TBI (Mathias et al., 2004; Yuan et al., 2007). Salmond and colleagues (2006), for example, using DTI in patients with chronic TBI, found significant changes in white matter integrity at 6 months postinjury. These changes involved an extensive reduction in anisotropy (a measure of the proportion of diffusion in the direction parallel to the long axis of the white matter tract) and increase in diffusivity (a measure of the magnitude of the diffusion) (Salmond et al., 2006). Another recent study compared changes in white matter tracts and cognitive functions in adults with mild, moderate, and severe TBI at 10 years postinjury. Compared to healthy controls, patients with moderate and severe TBI showed decreases in white matter anisotropy throughout the brain (Kraus et al., 2007).
Recovery course The natural recovery process after TBI is dependent upon the level of injury severity (mild, moderate, or severe). Patients with mild TBI typically return to their preinjury cognitive level within 3–6 months postinjury (Schretlen and Shapiro, 2003; Belanger et al., 2005). Conversely, patients with moderate and severe TBI recover slowly and frequently do not return to their preinjury cognitive level (Dikmen et al., 2003). Although recovery is associated with injury severity, it is important to remember that each recovery is an individualized process that depends on many other factors, such as age, general health, preinjury cognitive functioning (Raymont et al., 2008), psychiatric comorbidities, social environment (family, friends, work), and PTA duration. The combination of these factors determines the pattern of recovery from TBI, as shown in Figure 37.1 (Faul et al., 2010b). Generally, 85–95% of persons who have suffered a mild TBI will make a complete recovery, as compared to 60% of those who have experienced a moderate
Fig. 37.1. Typical temporal course of recovery in mild, moderate, and severe traumatic brain injury (TBI).
TBI and 15–20% of those who have experienced a severe TBI. Most patients with mild TBI recover in 3 months. Recent studies showed that the majority of patients with mild TBI recovered, but between 5% and 15% retained long-lasting impairments (Faul et al., 2010b). The likelihood of developing such long-term impairments increases when neuroimaging examination reveals structural/functional damage during the acute phase of the injury. Patients with this type of damage comprise a subcategory of mild TBI termed “complicated mild TBI,” and often continue to show symptoms of cognitive impairment over 6 months following the injury (Williams et al., 1990). Patients with moderate to severe TBI often exhibit persisting disability and cognitive impairments. A recent study found that, at 1 year postinjury, 47% of hospitalized patients reported functional difficulties (Pickelsimer et al., 2006). Another study indicated that 24% of patients hospitalized for moderate-severe TBI failed to return to work 1 year after the injury (Whiteneck et al., 2004). Similarly, a study on brain injury in Vietnam veterans reported that only 56% of participants with penetrating TBI were employed at 15 years postinjury, compared with 82 % of nonphysically injured veterans (Schwab et al., 1993). In addition to cognitive and functional impairment, patients with moderate and severe TBI also show higher rates of psychopathology (e.g., depression) in comparison to matched controls (Vanderploeg et al., 2007a).
COGNITIVE SEQUELAE OF TRAUMATIC BRAIN INJURY Functional and structural brain damage cause various neuropsychological impairments, including reductions in information processing speed, memory, as well as deficits in attention and executive functioning (Hopkins et al., 2005; O’Jile et al., 2006; Benson et al.,
TRAUMATIC BRAIN INJURY AND COGNITION 583 2007; Mathias and Wheaton, 2007; Fleminger, 2008). deficits associated with closed TBI can vary according Impairments in executive functioning affect mental to the TBI classification as mild or moderate-severe, flexibility, planning, self-monitoring, and problem solvas described below. ing (Bigler, 2007). Longitudinal studies on cognitive sequelae after TBI Mild closed traumatic brain injury can provide a better understanding of the time course of In a classic study examining longitudinal outcomes in recovery (Levin et al., 1990; Novack et al., 2000). Imporpatients with mild closed TBI, Dikmen and collaborators tantly, if performance on multiple cognitive tasks is fol(1986) tested cognitive ability at both 1 month and 1 year lowed over the course of recovery, researchers can then after injury. Patients in this study had a GCS score equal identify those tasks that best predict long-term outcomes to or greater than 12, an LOC of less than 1 hour, a PTA (see Ch. 29 for a detailed discussion on factors predicting of at least 1 hour, with no clinical evidence of brain outcome after TBI). Indeed, performance on neuropsycontusion. At 1 month after the injury, patients with mild chological tests 1 year after a severe TBI has been related TBI performed worse than matched controls in tests of to neuropsychological performance during the acute attention and memory (the Seashore Rhythm Test and phase of injury (Levin et al., 1990; Novack et al., the Selective Reminding Test); however, patients did 2000). For instance, Levin and collaborators (1990) not show impairments on other cognitive tasks, such showed that neuropsychological deficits in memory as the Trail Making Test and Wechsler Memory Scale. and information processing speed could persist at 1 year At 1 year after the injury, there were no significant postinjury, whereas language and visuospatial functions differences between mild TBI patients and control had recovered by that time (Levin et al., 1990). The same participants on any cognitive task. In a similar study, study established that lower GCS scores and pupillary Dikmen and collaborators (1987) examined the relationreactivity immediately following the injury predicted ship between injury severity and memory in patients with neuropsychological task performance at 1 year postinmild to moderate closed TBI, in comparison with jury. Novack and collaborators (2000) examined a more matched controls (Dikmen et al., 1987). Memory funcdetailed time course of TBI recovery, with neuropsychotion was assessed using the Wechsler Memory Scale logical assessments administered to TBI patients at and the Selective Reminding Test at 1 and 12 months 1 month intervals, between 6 and 12 months after injury. after the head injury. On average, patients with TBI Over the course of these 6 months, TBI patients showed had lower scores than the control participants on each consistent improvements in memory skills, speed prosubscale of the Wechsler Memory Scale and the Selective cessing and language, as well as community integration Reminding Test, at 1 month following the injury. Simiand quality of their daily life activities (Novack et al., larly, at 12 months, TBI patients showed increased scores 2000). Results from these types of studies are critical on most subscales of both tests, on average. However, in predicting the cognitive, behavioral, and emotional TBI patients with prolonged impaired consciousness time course of recovery after TBI. (PTA
