Does Early Age at Brain Insult Predict Worse Outcome? Neuropsychological Implications

Vicki Anderson, PhD; Rani Jacobs, PhD; Megan Spencer-Smith, PhD; Lee Coleman, MD; Peter Anderson, PhD; Jackie Williams, PhD; Mardee Greenham, BA (Hons); Rick Leventer, PhD


J Pediatr Psychol. 2010;35(7):716-727. 

In This Article

Abstract and Introduction


Objective Traditionally early brain insult (EBI) has been argued to have better outcome than later injury, consistent with the notion that the young brain is flexible and able to reorganize. This view was investigated by comparing neurobehavioral outcomes of children sustaining EBI at different developmental stages (gestation to late childhood).
Methods One hundred and sixty four children who had sustained focal brain insult (confirmed by MRI) formed six groups, based on age at EBI, (a) Congenital; (b) Peri-natal; (c) Infancy; (d) Preschool; (e) Middle Childhood; (f) Late Childhood, and were compared on a range of standardized neurobehavioral measures. Groups were matched for lesion characteristics and demographics.
Results Children sustaining EBI before age 2 recorded global deficits, while children with later EBI performed closer to average.
Conclusion These results question the advantages of early brain plasticity, demonstrating poorer outcome from very early insults, and increasingly better function with lesions later in childhood.


Recovery from early brain insult (EBI) is variable and unpredictable. Children with focal left-hemisphere insult, for example, may demonstrate age appropriate language abilities, free from the symptoms of aphasia observed following similar lesions in adulthood (Ballantyne, Spilkin, Hesselink, & Trauner, 2008; Ballantyne, Spilkin, & Trauner, 2007; Heywood & Canavan, 1987; Taylor & Alden, 1997). In contrast, generalized cerebral insult may result in poorer outcome in children than in adults suffering similar insults (Duval et al., 2009; Glosser, Cole, French, Saykin, & Sperling, 1997; Hessen, Anderson, & Nestvold, 2007; Mosch, Max, & Tranel, 2005; Strauss et al., 1995), with greatest deficits seen in "fluid" skills such as attention, information processing and executive skills.

Recent research has explored a range of factors that might influence recovery, and thus predict either "good" or "poor" outcomes. Apart from the well-established relationship between insult severity and outcome, and presence of epilepsy and poor prognosis, studies have failed to identify consistent links between underlying brain pathology and recovery within the pediatric domain (e.g., location, extent, laterality, neurological signs) (Ballantyne et al., 2007; Bates et al., 2001; Chilosi et al., 2005; Hertz-Pannier et al., 2002; Stiles et al., 2008). There is emerging evidence regarding the impact of pre-insult child function and environmental parameters (e.g., socio-demographics, access to interventions, parent/family function) (Anderson et al., 2006; Breslau, 1990; Catroppa, Anderson, Morse, Haritou, & Rosenfeld, 2008; Taylor et al., 2002). However, it remains unclear whether these factors are specific to particular outcome domains or have greater influence at particular developmental stages or times post insult (Catroppa & Anderson, 2008; Giza & Prins, 2006).

The developmental stage of the child at time of insult also influences outcome, although the direction of this influence is hotly debated. It is generally agreed that the young brain possesses greater plasticity and is less functionally committed than the adult brain, however the relative advantage that this provides is unclear (Giza & Prins, 2006; Johnston, 2009). Early plasticity theorists argue that the flexibility of young brain renders it more able to reorganize in response to injury (Ballantyne et al, 2007; 2008; Huttenlocher & Dabholkar, 1997; Kennard, 1936, 1940). In contrast, early vulnerability proponents postulate that the young brain is uniquely sensitive to insult, and that, if a cerebral region is damaged at a critical stage of cognitive development, functions dependent on that region will be irreversibly impaired (Hebb, 1942, 1949; Kolb, 1995; Luciana, 2003).

The young brain does have some capacity for neural restitution, via either neural regrowth or anatomical reorganization, although the time frame for this "window of opportunity" appears limited, probably to the preschool years (Giza & Prins, 2006; Johnson, 2005; Kolb, Pellis, & Robinson, 2004; Lenneberg, 1967). Even when such processes occur, full recovery may be limited by either: (1) establishment of inappropriate connections (Giza & Prins, 2006; Kolb et al., 2004; Stein & Hoffman, 2003) resulting in dysfunctional behavioral recovery; or (2) a "crowding effect" (Aram & Eisele, 1994; Vargha-Khadem, Isaacs, van der Werf, Robb, & Wilson, 1992), where functions normally subsumed by damaged tissue are crowded into remaining healthy brain areas, with a general depression of all abilities (Anderson et al., 1997; Duchowny et al., 1996; Ewing-Cobbs et al., 1997; Jacobs, Harvey, & Anderson, 2007; Leventer et al., 1999; Riva & Cazzaniga, 1986).

While there is growing consensus that developmental factors play a central role in outcome from EBI, the challenge remains to describe the nature of this relationship. To date, most research has focussed on specific conditions (e.g., stroke, traumatic brain injury), with varied findings (Anderson et al., 1997, 2005; Ballantyne et al., 2008; Duchowny et al., 1996; Vargha-Khadem et al., 1992). The picture is now consistent with respect to insults causing diffuse pathology, where there is limited healthy brain tissue to support plasticity processes, and where outcomes from early insults are usually poor (Anderson et al, 2005; Ewing-Cobbs, Barnes, & Fletcher, 2003). In contrast, findings from studies of children with focal lesions, where there may be healthy tissue available for reorganization, are conflicting (Ballantyne et al, 2007; 2008; Stiles, 2008). While this "condition-specific" approach has contributed to our understanding of developmental influences, it is unable to address age at insult effects across gestation and childhood, as very few conditions occur across the developmental spectrum. To comprehensively examine the impact of insult to the developing brain, it is necessary to explore conditions occurring both pre- and post-natally. Further, studies incorporating both neural and behavioral domains and their developmental processes will be of particular value.

Both brain maturation and cognitive development occur in the step-wise manner, where critical periods of rapid progress occur (Casey, Giedd, & Thomas, 2000; Flavell, 1992; Gogtay et al., 2004; Klingberg, Vaidya, Gabrieli, Moseley, & Hedehus, 1999; Piaget, 1963), separated by more stable periods. Disruption during these critical periods may cause "flow on" effects, as the establishment of other, later emerging, neural connections and functional skills is thrown off course (Mosch, Max, & Tranel, 2005; Thomas & Johnson, 2008). Animal research supports this view, describing different outcomes depending on the neural processes underway at the time of insult (Kolb et al., 2004). Similarly, cognitive theorists argue that skills in a rapid phase of development will be most vulnerable to the impact of central nervous system (CNS) insult (Catroppa et al., 2008; Dennis, 1989).

This study examines outcomes from EBI sustained across gestation and childhood. We constructed six "age at lesion" (AL) groups, defined according to developmental timetables for key neurological processes in the CNS as well as developmental timetables for cognitive processes (Anderson, 1998; Anderson, Anderson, Northam, Jacobs, & Catroppa, 2001; Anderson & Lajoie, 1996; Dennis, 1989; Kolb et al., 2004; Pavlovic et al., 2006; Smidt, Jacobs, & Anderson, 2004). These studies suggest that both neurologic and cognitive developmental processes occurring at the time of brain insult are central to outcome. Of note, AL groups were necessarily heterogeneous for cause of insult as many CNS insults occur only at specific stages of development (e.g., penetrating head injury, developmental malformations). To minimize any confounding effects caused by this heterogeneity: (1) only children identified as having focal abnormalities on MRI scan were included in the sample; and (2) AL groups were compared with respect to lesion characteristics (size, location, laterality).

We addressed the early plasticity-early vulnerability debate by posing the following two hypotheses: (1) When compared to population expectations, children with EBI would display global neurobehavioral deficits impacting language, visuo-spatial skills, attention, memory, EF and processing speed; and (2) age at brain insult would have long-term implications for neurobehavioral outcome: (a) for language and visuospatial domains, which are established early in childhood, we expected children with lesions before or at age 2 years would perform worse than those with insults after age 2; (b) for attention and EF, skills with major growth spurts around 12 months and 5 years, we predicted that children with lesion ≤age 2 years would perform poorest, followed by those with lesions between 3 and 6 years, with older age at lesion best; and (c) for memory and processing speed, which show incremental development throughout childhood, we expected an overall effect of age at lesion, with differences across specific groups not sufficient to reach significance.


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