White matter and information processing speed following treatment with cranial-spinal radiation for pediatric brain tumor.

OBJECTIVE: We compared the structure of specific white matter tracts and information processing speed between children treated for posterior fossa tumors with cranial-spinal radiation (n = 30), or with surgery +/- focal radiation (n = 29), and healthy children (n = 37). METHOD: Probabilistic diffusion tensor imaging (DTI) tractography was used to delineate the inferior longitudinal fasciculi, optic radiation, inferior frontal occipital fasciculi, and uncinate fasciculi bilaterally. Information processing speed was measured using the coding and symbol search subtests of the Wechsler Intelligence Scales, and visual matching, pair cancellation, and rapid picture naming subtests of the Woodcock-Johnson Test of Cognitive Ability, 3rd revision. We examined group differences using repeated measures MANOVAs and path analyses were used to test the relations between treatment, white matter structure of the tracts, and information processing speed. RESULTS: DTI indices of the optic radiations, the inferior longitudinal fasciculi, and the inferior fronto-occipital fasciculi differed between children treated with cranial-spinal radiation and children treated with surgery +/- focal radiation, and healthy controls (p = .045). Children treated with cranial-spinal radiation also exhibited lower processing speed scores relative to healthy control subjects (p = .002). Notably, we observed that group differences in information processing speed were related to the structure of the right optic radiation (p = .002). CONCLUSION: We show that cranial-spinal radiation may have a negative impact on information processing speed via insult to the right optic radiations. (PsycINFO Database Record

White matter compromise predicts poor intellectual outcome in survivors of pediatric low-grade glioma.

BACKGROUND: While the impact of cranial radiation on white matter following treatment for pediatric brain tumor has been the focus of many recent studies, the effect of treatment in the absence of radiation has received little attention. The relations between white matter and cognitive outcome have not been explored in patients who have undergone radiation-free treatment. As most patients treated without cranial radiation survive long after their diagnosis, it is critical to identify factors that may impact structural and neurocognitive outcomes. METHODS: Using diffusion tensor imaging, we examined white matter structure in 32 patients with pediatric low-grade glioma (PLGG) (19 with subtentorial location and 13 with supratentorial location) and 32 healthy participants. Indices of intellectual functioning were also evaluated. Radiation was not used to treat this cohort, aged 8-19 years. RESULTS: We detected evidence of deficits in IQ and compromised supra- and subtentorial white matter in patients relative to healthy children (P < .05). Compromise of supratentorial white matter mediated the impact of treatment for PLGG on IQ. Greater white matter compromise was observed in patients who presented without multiple symptoms, were treated with biopsy/no surgery, had positive neurofibromatosis 1 status, were younger age at diagnosis, and whose parents had lower levels of education (P < .05). CONCLUSIONS: Our findings provide evidence of increased risk of intellectual and white matter compromise in patients treated for PLGG without radiation. We identify a neural origin of cognitive deficit useful for predicting outcome and mitigating long-term adverse effects in pediatric brain tumor patients treated without cranial radiation.

Neuropsychological late effects of treatment for acute leukemia in children with Down syndrome.

BACKGROUND: Children with Down syndrome (DS) have an elevated risk of developing acute leukemia, but little is known about treatment-related neuropsychological morbidity because they are systematically excluded from research in this area. The current study investigated neuropsychological outcomes in children with DS treated for acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) compared to children with DS with no history of cancer. PROCEDURE: Participants were 4 to 17 years of age at testing and were administered measures of intelligence, academic achievement, language, visual-motor and fine-motor skills, and adaptive function. Patients had been off treatment for at least 2 years. RESULTS: The AML group (N = 12) had significantly lower verbal intelligence and receptive vocabulary compared to controls (N = 21). By contrast, the ALL group (N = 14) performed significantly worse than controls on measures of verbal intelligence, spelling, receptive and expressive vocabulary, visual-motor skills, and adaptive function. CONCLUSIONS: Patients with DS treated for AML may have specific post-treatment morbidity in verbal function, whereas those treated for ALL have broader morbidity affecting multiple neuropsychological domains and overall adaptive function. We hypothesize that the broader impairment profile of ALL survivors may be related to a combination of the longer duration of central nervous system-directed treatment for ALL compared to AML and the concomitant limited access to intervention opportunities during active treatment.

Brain lesions and IQ: recovery versus decline depends on age of onset.

A growing literature suggests that early lesions are associated with poorer IQ outcome. Those studies covered a restricted age range in pediatric populations only and did not control for important moderator variables. The present investigation studied IQ change in brain-lesioned children and adults (age 0 to 84 years). Altogether, 725 cases with a documented unilateral focal lesion were gathered from hospital charts and from published cases in the literature, including 240 with repeated IQ testing. Multiple regression analyses isolated the contribution of age at lesion onset to IQ change. Important mediator variables included were lesion side, site, volume, etiology, and so on. An early lesion was significantly associated with poorer postlesion IQ in time and with decline of IQ in time. Later onset lesions were associated with better postlesion IQ and recovery in time. The so-called Kennard principle is refuted, with regard to IQ.

Cognitive changes in children treated for acute lymphoblastic leukemia with chemotherapy only according to the Pediatric Oncology Group 9605 protocol.

The purpose of this study was to examine cognitive functioning and neuroimaging in children with leukemia treated with the Pediatric Oncology Group 9605 protocol at the Children's Hospital of Eastern Ontario. Mean age at diagnosis was 4.88 +/- 2.54 years. The mean (n = 24) Wechsler Verbal and Performance IQ fell in the low-average range (87.33 +/- 15.69 and 84.83 +/- 19.11, respectively). Mean (n = 20) Verbal and Visual Memory Indexes of 82.95 +/- 15.46 and 88.30+/- 10.80, respectively, were obtained. The proportion of scores on measures of intelligence and memory falling > 1 SD below the normative mean was substantially higher than expected. Paired t-test suggested that Wechsler Verbal IQ and memory remained stable, whereas Wechsler Performance IQ declined significantly. The results of growth curve analyses replicated these findings and suggested a significant adverse effect of cumulative dosage of intrathecal methotrexate on estimated Wechsler Performance IQ. Although only two children experienced seizures, 78% of the group showed leukoencephalopathy on at least one magnetic resonance image. Reliance on seizures as a predictor of leukoencephalopathy might underestimate the incidence of neurotoxicity.

Predictors of intellectual function after a unilateral cortical lesion: study of 635 patients from infancy to adulthood.

This study investigated potential predictors of intellectual outcome in 417 children and 218 adults who had sustained a unilateral cortical lesion. Of these, 295 cases were collected from the scientific literature and 340 from medical records at seven hospitals in Canada Different sets of predictors emerged for the Wechsler Verbal and Performance IQ values, accounting for differing variances (i.e., 12.4% and 20.1%, respectively). The volume of the lesion was the factor that explained the most variance (i.e., 4.95% and 11.7%, respectively). Age at lesion onset was significantly and positively correlated with verbal intelligence scores. This variable, considered independently or in interaction with other predictors, did not account for a large portion of the variance explained in intelligence. This refutes the commonly held notion that early onset of the insults results in a better prognosis.