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Background Neurocognitive sequelae following treatment for pediatric acute lymphoblastic leukemia (ALL) has been reported in a significant proportion of survivors, including those treated only with chemotherapy. Early identification of children “at risk” for neurocognitive problems is not yet reliable. Biomarkers of oxidative stress (e.g., oxidated phosphatidylcholine) in cerebral spinal fluid (CSF) have been correlated with intensity of methotrexate (MTX) treatment, suggesting an association with acute central nervous system toxicity. Procedure This study examined the association between oxidized CSF phospholipids and executive functions throughout chemotherapy. Measures of oxidative stress and executive functions were examined in 88 children newly diagnosed with ALL. The children were followed over three years with neurocognitive testing and parent ratings of executive functions. Results Results demonstrated an association between increased oxidative stress following induction and consolidation and decreased executive function two years later. Younger age at diagnosis was associated with both an increase in oxidative stress and in executive dysfunction; younger age was associated with poorer ability to organize materials in one's environment (r(48) = 0.28, p < 0.05) and with greater oxidated phosphatidylcholine in CSF at the end of chemotherapy ( r(48) = −0.27, p < 0.05). As such, younger age appears to be the most prominent moderator of neurocognitive decline. Conclusions These results link functional changes to CSF biomarkers and underscore the importance of monitoring cognitive development in young children treated for ALL. Children with less advanced central nervous system development may be particularly vulnerable to the effects of chemotherapy.

Recent factor-analytic studies of the Halstead Category Test (HCT) indicate that its seven subtests form three factors including a Counting factor (subtests I and II), a Spatial Positional Reasoning factor (subtests III, IV, and VII), and a Proportional Reasoning factor (subtests V, VI, and VII). The sensitivity and specificity of these factors to heterogeneous forms of brain damage was examined in a large sample of patients and a normal comparison sample. A prorated Impairment Index, which excluded the HCT error score, was used to assign participants with brain damage into mild, moderate, and severe impairment groups. Also, groups with various forms of neuropathology were contrasted. Results indicated that both the Spatial Positional Reasoning and the Proportional Reasoning factors were sensitive to brain damage. However, in all of the brain-damage groups, a greater percentage of errors were made on the Spatial Positional factor, suggesting that of the two it was more difficult for those with brain damage. The sensitivity and specificity of the Spatial Positional factor score for detection of brain damage was comparable to that of the total error score, which has been previously demonstrated to be an excellent indicator of brain damage. Findings provide further support for the validity of the HCT factors, and are consistent with the view that factor scores may be useful in interpreting the HCT.

Developing embedded indicators of suboptimal effort on objective neurocognitive testing is essential for detecting increasingly sophisticated forms of symptom feigning. The current study explored whether Symbol Span, a novel Wechsler Memory Scale-fourth edition measure of supraspan visual attention, could be used to discriminate adequate effort from suboptimal effort. Archival data were collected from 136 veterans classified into Poor Effort (n = 42) and Good Effort (n = 94) groups based on symptom validity test (SVT) performance. The Poor Effort group had significantly lower raw scores (p < .001) and age-corrected scaled scores (p < .001) than the Good Effort group on the Symbol Span test. A raw score cutoff of <14 produced 83% specificity and 50% sensitivity for detection of Poor Effort. Similarly, sensitivity was 52% and specificity was 84% when employing a cutoff of <7 for Age-Corrected Scale Score. Collectively, present results suggest that Symbol Span can effectively differentiate veterans with multiple failures on established free-standing and embedded SVTs.

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