Developmental model relating white matter volume to neurocognitive deficits in pediatric brain tumor survivors

Abstract

BACKGROUNDThe primary objective of this study was to test the hypothesis that, among survivors of pediatric brain tumors, the association between reduced volumes of normal‐appearing white matter (NAWM) and intellectual/academic achievement deficits can be explained by patient problems with memory and attention.METHODSQuantitative tissue volumes from magnetic resonance imaging scans and neurocognitive assessments were obtained for 40 long‐term survivors of pediatric brain tumors. They were treated with radiotherapy (RT) with or without chemotherapy 2.6–15.3 years earlier (median, 5.7 years) at an age of 1.7–14.8 years (median, 6.5 years). Neurocognitive assessments included standardized tests of intellect (intelligence quotient [IQ]), attention, memory, and academic achievement.RESULTSAnalyses revealed significant impairments in patients' neurocognitive test performance on all measures. After statistically controlling for age at RT and time from RT, significant associations were found between NAWM volumes and both attentional abilities and IQ, and between attentional abilities and IQ. Subsequent analyses supported the hypothesis that attentional abilities, but not memory, could explain a significant amount of the relationship between NAWM and IQ. The final developmental model predicting academic achievement based on NAWM, attentional abilities, and IQ explained approximately 60% of the variance in reading and spelling and almost 80% of the variance in math.CONCLUSIONSThe authors demonstrated that the primary consequence of reduced NAWM among pediatric patients treated for brain tumors was decreased attentional abilities, leading to declining IQ and academic achievement. Cancer 2003;10:2512–9. © 2003 American Cancer Society.DOI 10.1002/cncr.11355

Brain structural abnormalities in survivors of pediatric posterior fossa brain tumors: A voxel-based morphometry study using free-form deformation

“…The WM abnormalities identified in this study are consistent with the previous ROI-based findings in PFBT survivors (Palmer et al, 2002;Reddick et al, 2003;Reddick et al, 2005). A region of high variability beneath the corpus callosum and associated with the third ventricle was observed, even on the spatially normalized images of the PFBT group, implying that the morphological differences identified in WM could be caused, at least in part, by the residual effects of enlarged ventricles.…”

“…Therefore, the success of VBM largely depends on the extent to which the brain structural abnormalities can be contrasted with this single-imaging modality. Reddick and colleagues have demonstrated the benefit of using multiple contrast images such as T1-weighted, T2-weighted, FLAIR, and proton density-weighted MR images to investigate morphological abnormalities (Reddick et al, 2003;Reddick et al, 2005) in cancer survivors. VBM analysis of a multi-contrast image data set may provide a more sensitive and specific tool for identifying morphological abnormalities in this patient population.…”

“…Many studies have investigated the association between CNS-directed treatment and structural damage of the brain. Brain structural changes such as atrophy from gray and white matter loss or developmental deficits in the corpus callosum that are known to occur after CNS-directed treatments have been correlated with cognitive deficits (Macedoni-Luksic et al, 2003;Mulhern et al, 1999;Mulhern et al, 2001;Palmer et al, 2002;Reddick et al, 2003;Reddick et al, 2005;Steen et al, 2001), but the specific neural substrates of those deficits are largely unknown. Neuroimaging techniques, including functional MRI (fMRI) and diffusion tensor imaging (DTI), are promising new tools to investigate brain structure and function in such patients Phillips et al, 2005;Ries et al, 2004;Zou et al, 2005).…”

Irradiation-induced progenitor cell death in the developing brain is resistant to erythropoietin treatment and caspase inhibition

“…: nonsignificant, using Student's unpaired t-test development. 2,26 Using the LQ model 27 and an a/b ratio of 3 for late effects in the normal brain tissue, the acute exposures of 4, 8 and 12 Gy are equivalent to approximately 6, 18 and 43 Gy, respectively, when delivered in repeated 2 Gy fractions. These dose levels represent clinically relevant doses, that is, 10, 30 and 80% isodoses in radical radiotherapy of malignant brain tumors in children.…”

Changes in Cerebral Cortex of Children Treated for Medulloblastoma

“…The decrease in the amount of normalappearing white matter also correlated with the craniospinal radiation dose (24). Decreased amounts of normalappearing white matter correlated with decreases in fullscale intelligence quotient (IQ), factual knowledge, verbal thinking, nonverbal thinking, attention, and academic achievement (22,23,25).…”