Timing of TBI in Childhood and Intellectual Outcome
Timing of TBI in Childhood and Intellectual Outcome
Objective Typically, studies on outcomes after traumatic brain injury (TBI) have investigated whether a younger age at injury is associated with poorer recovery by comparing 2 age groups rather than participants injured across childhood. This study extended previous research by examining whether the influence of age on recovery fits an early vulnerability or critical developmental periods model.
Methods Children with a TBI (n = 181) were categorized into 4 age-at-injury groups—infant, preschool, middle childhood, and late childhood—and were evaluated at least 2-years post-TBI on IQ.
Results Overall, the middle childhood group had lower IQ scores across all domains. Infant and preschool groups performed below the late childhood group on nonverbal and processing speed domains.
Conclusions Contrary to expectations, children injured in middle childhood demonstrated the poorest outcomes; this age potentially coincides with a critical period of brain and cognitive development.
Traumatic brain injury (TBI) is a major cause of disability in children (Kraus, Rock, & Hemyari, 1990). An extensive body of research has demonstrated that TBI results in impaired cognition, with recovery influenced by individual characteristics, injury, and environmental factors (Anderson et al., 2006; Catroppa, Anderson, Morse, Haritou, & Rosenfeld, 2008). Understanding the influence of these factors is of great interest to both clinicians and researchers. In terms of injury factors, increased injury severity is a well-established predictor of cognitive sequelae (Anderson, Morse, Catroppa, Haritou, & Rosenfeld, 2004; Anderson, Catroppa, Morse, Haritou & Rosenfeld, 2005; Ewing-Cobbs, Fletcher, Levin, Iovino, & Miner, 1998; Ewing-Cobbs et al., 2006). Environmental factors, including low socioeconomic status (SES), dysfunctional family environments, and reduced access to resources, are also associated with poorer cognitive recovery (Taylor et al., 2001). It appears that environment interacts with injury severity to influence outcomes. This theory is referred to as the "double-hazard theory", which states that while severe TBI is associated with the poorest outcomes, severe TBI coupled with a family of social disadvantage or dysfunction has the worst functional outcomes (Escalona, 1982). In contrast, the presence of only one of these factors, either severe TBI or environmental risk factors (social disadvantage/family dysfunction) is linked to significantly better recovery (Anderson et al., 2005; Escalona, 1982; Taylor & Alden, 1997).
Individual characteristics, such as gender, age, and pre-injury function, also influence outcome. Relevant to the present study, the impact of age at injury has been a focus of several research studies, with varied results. Those arguing for the importance of age at injury propose that poor outcomes are explained by the incomplete development of the brain in early life, with a TBI derailing ongoing maturational processes and leading to neurobehavioral impairment (Anderson et al., 2005; Ewing-Cobbs, Miner, Fletcher, & Levin, 1989). Childhood is indeed a time of rapid brain development. In the first two years of life processes, such as dendritization and synaptogenesis are highly active. Further, from birth and during critical periods through childhood, the brain undergoes extensive myelination, particularly in the anterior and subcortical regions (Spencer-Smith & Anderson, 2009; Stiles, 2000). Early in childhood, while these processes are ongoing, the brain is less functional committed than an adult brain, with researchers arguing that this greater plasticity leads to an increased ability to recover after insult, referred to as early plasticity theory (Kennard, 1936; Teuber, 1971). While this view is supported by focal lesion and hemispherectomy studies (Ballantyne, Spilkin, Hesselink, & Trauner, 2008; Dennis & Whitaker, 1976; Hertz-Pannier et al., 2002), when damage is diffuse with little healthy tissue available for compensation (such as in TBI), early plasticity theories are insufficient to explain recovery patterns.
In response to these limitations, the early vulnerability theory was suggested, proposing that the young brain is more susceptible to damage and associated cognitive impairment, particularly in the context of diffuse injury such as TBI (Anderson & Moore, 1995; Donders & Warschausky, 2007; Hebb, 1942; Kriel, Krach, & Panser, 1989). Young children and infants are particularly vulnerable to damage after TBI for physiological and neurological reasons, for example, a thin and pliable skull, a disproportionately large and heavy head with weak neck muscles increasing susceptibility to rotational and shearing forces and increased elasticity of blood vessels (Case, 2008; Hahn, Chyung, Barthel, Bailes, Flannery & McLone, 1988; Margulies & Thibault, 2000).
Despite this growing literature, as yet there is no consensus concerning the specific age range that characterizes this early vulnerability. For example, one study comparing children injured <1 year of age to children injured between 1 and 2 years found no difference in outcomes (Keenan, Runyan, & Nocera, 2006). Similarly, Ewing-Cobbs et al. (1997) compared children injured at a between 4 and 41 months to those injured at 42–72 months and also reported no age-at-injury effect. In contrast, our team has repeatedly demonstrated poorer outcomes for children aged <7 years compared to older children (Anderson & Moore, 1995; Anderson et al, 2005). While methodological differences may underpin these contradictory results, it may be that the assumption of a linear relationship between age at injury and outcome is not appropriate. This possibility is consistent with the principles of developmental biology that characterize early brain development as a stepwise process consisting of peaks and plateaus, often termed critical periods, during which neural maturation is rapid and neural networks are consolidated (Hudspeth & Pribram, 1990; Kolb, Pellis, & Robinson, 2004). Interruption of these processes via injury has been reported to have a dramatic impact, although the details of these processes remain far from precise. Recent studies examining the functional consequences of these developmental processes has provided limited support for a linear age at injury effect but has highlighted the significant vulnerability of the brain prior to 2 years of age (Anderson et al., 2009), which is a period of increased dendritization and synaptogenesis (Huttenlocher, 1979; Huttenlocher & Dabholkar, 1997) and when many cognitive skills begin to develop.
This study extended previous research by examining the impact of age at insult in a sample aged two months to 12 years at injury, divided across four developmental stages, in order to explore whether recovery from TBI is best represented by an early vulnerability model with earlier injury associated with poorest outcome or a critical period model with recovery dependent on neurological and cognitive development at time of injury. This follow-up time was chosen to ensure that early recovery processes had stabilized and so that even the youngest children could be tested using the Wechsler Scales. Drawing from past research, the following hypotheses were developed. First, we expected that children with severe TBI would record the lowest IQ scores. Second, consistent with the majority of literature available, we expected that very early injuries (<2 years) would be associated with the greatest IQ deficits, and conversely, late child injury (10–12 years) would be associated with fewer IQ impairments. There is little empirical research to guide hypotheses for preschool and middle childhood insults (3–9 years), but we speculated that, due to growth spurts from 6 to 9 years (Huttenlocher, 1979; Huttenlocher & Dabholkar, 1997; Kolb et al., 2004), this age group would also be vulnerable to poor outcome. Third, we predicted that findings would support the "double-hazard" theory: that is, severe TBI and social disadvantage or family dysfunction would be associated with the poorest performance. The role of injury and environmental factors, such as SES and family function, were also examined to explore their contribution to outcome.
Abstract and Introduction
Abstract
Objective Typically, studies on outcomes after traumatic brain injury (TBI) have investigated whether a younger age at injury is associated with poorer recovery by comparing 2 age groups rather than participants injured across childhood. This study extended previous research by examining whether the influence of age on recovery fits an early vulnerability or critical developmental periods model.
Methods Children with a TBI (n = 181) were categorized into 4 age-at-injury groups—infant, preschool, middle childhood, and late childhood—and were evaluated at least 2-years post-TBI on IQ.
Results Overall, the middle childhood group had lower IQ scores across all domains. Infant and preschool groups performed below the late childhood group on nonverbal and processing speed domains.
Conclusions Contrary to expectations, children injured in middle childhood demonstrated the poorest outcomes; this age potentially coincides with a critical period of brain and cognitive development.
Introduction
Traumatic brain injury (TBI) is a major cause of disability in children (Kraus, Rock, & Hemyari, 1990). An extensive body of research has demonstrated that TBI results in impaired cognition, with recovery influenced by individual characteristics, injury, and environmental factors (Anderson et al., 2006; Catroppa, Anderson, Morse, Haritou, & Rosenfeld, 2008). Understanding the influence of these factors is of great interest to both clinicians and researchers. In terms of injury factors, increased injury severity is a well-established predictor of cognitive sequelae (Anderson, Morse, Catroppa, Haritou, & Rosenfeld, 2004; Anderson, Catroppa, Morse, Haritou & Rosenfeld, 2005; Ewing-Cobbs, Fletcher, Levin, Iovino, & Miner, 1998; Ewing-Cobbs et al., 2006). Environmental factors, including low socioeconomic status (SES), dysfunctional family environments, and reduced access to resources, are also associated with poorer cognitive recovery (Taylor et al., 2001). It appears that environment interacts with injury severity to influence outcomes. This theory is referred to as the "double-hazard theory", which states that while severe TBI is associated with the poorest outcomes, severe TBI coupled with a family of social disadvantage or dysfunction has the worst functional outcomes (Escalona, 1982). In contrast, the presence of only one of these factors, either severe TBI or environmental risk factors (social disadvantage/family dysfunction) is linked to significantly better recovery (Anderson et al., 2005; Escalona, 1982; Taylor & Alden, 1997).
Individual characteristics, such as gender, age, and pre-injury function, also influence outcome. Relevant to the present study, the impact of age at injury has been a focus of several research studies, with varied results. Those arguing for the importance of age at injury propose that poor outcomes are explained by the incomplete development of the brain in early life, with a TBI derailing ongoing maturational processes and leading to neurobehavioral impairment (Anderson et al., 2005; Ewing-Cobbs, Miner, Fletcher, & Levin, 1989). Childhood is indeed a time of rapid brain development. In the first two years of life processes, such as dendritization and synaptogenesis are highly active. Further, from birth and during critical periods through childhood, the brain undergoes extensive myelination, particularly in the anterior and subcortical regions (Spencer-Smith & Anderson, 2009; Stiles, 2000). Early in childhood, while these processes are ongoing, the brain is less functional committed than an adult brain, with researchers arguing that this greater plasticity leads to an increased ability to recover after insult, referred to as early plasticity theory (Kennard, 1936; Teuber, 1971). While this view is supported by focal lesion and hemispherectomy studies (Ballantyne, Spilkin, Hesselink, & Trauner, 2008; Dennis & Whitaker, 1976; Hertz-Pannier et al., 2002), when damage is diffuse with little healthy tissue available for compensation (such as in TBI), early plasticity theories are insufficient to explain recovery patterns.
In response to these limitations, the early vulnerability theory was suggested, proposing that the young brain is more susceptible to damage and associated cognitive impairment, particularly in the context of diffuse injury such as TBI (Anderson & Moore, 1995; Donders & Warschausky, 2007; Hebb, 1942; Kriel, Krach, & Panser, 1989). Young children and infants are particularly vulnerable to damage after TBI for physiological and neurological reasons, for example, a thin and pliable skull, a disproportionately large and heavy head with weak neck muscles increasing susceptibility to rotational and shearing forces and increased elasticity of blood vessels (Case, 2008; Hahn, Chyung, Barthel, Bailes, Flannery & McLone, 1988; Margulies & Thibault, 2000).
Despite this growing literature, as yet there is no consensus concerning the specific age range that characterizes this early vulnerability. For example, one study comparing children injured <1 year of age to children injured between 1 and 2 years found no difference in outcomes (Keenan, Runyan, & Nocera, 2006). Similarly, Ewing-Cobbs et al. (1997) compared children injured at a between 4 and 41 months to those injured at 42–72 months and also reported no age-at-injury effect. In contrast, our team has repeatedly demonstrated poorer outcomes for children aged <7 years compared to older children (Anderson & Moore, 1995; Anderson et al, 2005). While methodological differences may underpin these contradictory results, it may be that the assumption of a linear relationship between age at injury and outcome is not appropriate. This possibility is consistent with the principles of developmental biology that characterize early brain development as a stepwise process consisting of peaks and plateaus, often termed critical periods, during which neural maturation is rapid and neural networks are consolidated (Hudspeth & Pribram, 1990; Kolb, Pellis, & Robinson, 2004). Interruption of these processes via injury has been reported to have a dramatic impact, although the details of these processes remain far from precise. Recent studies examining the functional consequences of these developmental processes has provided limited support for a linear age at injury effect but has highlighted the significant vulnerability of the brain prior to 2 years of age (Anderson et al., 2009), which is a period of increased dendritization and synaptogenesis (Huttenlocher, 1979; Huttenlocher & Dabholkar, 1997) and when many cognitive skills begin to develop.
This study extended previous research by examining the impact of age at insult in a sample aged two months to 12 years at injury, divided across four developmental stages, in order to explore whether recovery from TBI is best represented by an early vulnerability model with earlier injury associated with poorest outcome or a critical period model with recovery dependent on neurological and cognitive development at time of injury. This follow-up time was chosen to ensure that early recovery processes had stabilized and so that even the youngest children could be tested using the Wechsler Scales. Drawing from past research, the following hypotheses were developed. First, we expected that children with severe TBI would record the lowest IQ scores. Second, consistent with the majority of literature available, we expected that very early injuries (<2 years) would be associated with the greatest IQ deficits, and conversely, late child injury (10–12 years) would be associated with fewer IQ impairments. There is little empirical research to guide hypotheses for preschool and middle childhood insults (3–9 years), but we speculated that, due to growth spurts from 6 to 9 years (Huttenlocher, 1979; Huttenlocher & Dabholkar, 1997; Kolb et al., 2004), this age group would also be vulnerable to poor outcome. Third, we predicted that findings would support the "double-hazard" theory: that is, severe TBI and social disadvantage or family dysfunction would be associated with the poorest performance. The role of injury and environmental factors, such as SES and family function, were also examined to explore their contribution to outcome.
Source...