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

Disclosures

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

In This Article

Discussion

With the aim of progressing the plasticity-early vulnerability debate this study explored neurobehavioral skills after EBI in children sustaining focal EBI during six different developmental periods, from gestation to late childhood. Comparisons between the total EBI sample and normative expectations supported our first prediction, that children with EBI are at increased risk of neurobehavioral impairment compared to healthy children. Significantly reduced skills were evident across all domains under study—language, visuo-spatial skills, memory, attention, executive skills, and processing speed. As predicted by our second hypothesis, outcomes differed significantly depending on age at insult, with preliminary evidence of some variation across domains, suggesting that different stages of brain development may be critical for the establishment of specific cognitive functions. Further, presence of seizures was associated with poorer performance across AL groups for language, visuo-spatial skills, memory, attention, and EF.

Do Children with EBI Differ from Population Expectations?

Children with EBI, as a group, performed significantly below population expectations for all domains studied, consistent with much previous research (Ewing-Cobbs et al., 1997; Jacobs et al., 2007). It is of interest to note that, despite these highly significant group differences, mean scores for the EBI group generally fell less than one standard deviation below expectations, representing performances hovering at the lower end of average. On 6/22 measures group means were greater than 1 SD from the mean, and for these measures, scores for >50% of the total sample fell below the normal range.

Does Age at Insult Influence Long-term Outcome?

Age at insult does affect long-term neurobehavioral outcome, although the relationship is complex. Initial examination of the data indicates that a linear relationship might explain age at insult and neurobehavioral outcome, at odds with animal model predictions (Kolb et al., 2004). Such an interpretation appears to be supported for memory and processing speed. However, the remainder of our findings (language, visuo-spatial, attention and EF domains) suggest that there is a significant discrepancy in skills between children with insults before age 2 years and those with insults sustained at 7 years or older, with EBI sustained before age 2 resulting in poorest results. In contrast, children with lesions after age 7 recorded better outcomes. This pattern is consistent with Dennis's (1989) prediction that disruption to neurobehavioral processes during the early stages of skill development will have maximal impact on outcome, while later insults, when skills are better established, will be less harmful.

These results support an early vulnerability perspective, with children sustaining serious focal brain insults prior to and around the time of birth and up to age 2 being most at risk for neurobehavioral deficits. Despite the documented focal nature of brain pathology, there was little evidence that this group had increased potential for reorganization of function, or recruitment of healthy brain regions to support recovery of function. Rather, findings suggested that it was children with insults in the second decade who were more likely to escape relatively unscathed.

When interpreting study findings, a number of potential limitations should be considered. First, this study recruited children based on AL rather than the traditional "diagnosis-based" approach. In doing so, the resultant sample included children for whom mechanism of insult varied, increasing the risk that findings might reflect differences in brain pathology rather than AL. To minimize this risk, we restricted participation to children with MRI documented focal lesions and collected detailed information regarding the location, laterality, and size of lesion. We believe that this approach has provided important data to assist in understanding the impact of EBI from an empirical perspective. Second, we employed a categorical approach to quantifying developmental stage. While these categories reflect CNS growth spurts, they are necessarily inexact and may mask specific critical developmental periods. Third, due to current privacy laws restricting researchers from accessing information on nonparticipating children we are unable to compare participating and non-participating children, and so we cannot be certain that our sample is representative of either children within each age at insult group or of all children with significant brain insult. Fourth, the cross-sectional nature of the study limited conclusions as to whether deficits identified represented a permanent deficit or a delay in skill development. To extend these findings, research with larger samples and including longitudinal follow-up is required. Finally, use of age standardized, normative data (and in a few instances raw scores or stanines), rather than an appropriately constructed healthy comparison group is a study limitation. Of importance, our results are consistent with previous research documenting the detrimental effects of brain insult sustained early in life (Anderson et al., 1997, 2005; Anderson & Moore, 1995; Chilosi et al., 2005; Ewing-Cobbs et al., 1997; Jacobs et al., 2007; Pavlovic et al., 2006), and provide little evidence to corroborate early plasticity notions, which argue for good outcome from EBI. Use of normative data does have an advantage over use of small, unrepresentative control samples (e.g., with inflated IQ scores) commonly reported in this field, which increase the risk of inaccurate characterization of the study results (Ballantyne et al, 2008).

In conclusion, our study supports the "early vulnerability model" for EBI. Results showed that, in comparison to population expectations, children with EBI were at increased risk for functional impairment across all domains assessed. Further, age at insult had a significant impact on outcome. While our findings were not entirely consistent with a linear relationship between age at insult and neurobehavioral outcomes, children sustaining EBI before age 2 years recorded more global and severe deficits, while children with later EBI, sustained at or after age 7, performed closer to normal expectations. Our results support the need for better access to diagnostic and early intervention services for children sustaining EBI, who have often been considered to have a low risk of long-term impairments. They also emphasize the importance of co-morbid seizures in children with EBI for long term neurobehavioral outcome.

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