Patterns of intellectual development among survivors of pediatric medulloblastoma: a longitudinal analysis.
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PURPOSE: To examine two competing hypotheses relating to intellectual loss among children treated for medulloblastoma (MB): Children with MB either: (1) lose previously learned skills and information; or (2) acquire new skills and information but at a rate slower than expected compared with healthy same-age peers. PATIENTS AND METHODS: Forty-four pediatric MB patients were evaluated who were treated with postoperative radiation therapy (XRT) with or without chemotherapy. After completion of XRT, a total of 150 examinations were conducted by use of the child version of the Wechsler Intelligence SCALES: These evaluations provided a measure of intellectual functioning called the estimated full-scale intelligence quotient (FSIQ). Changes in patient performance corrected for age (scaled scores) as well as the uncorrected performance (raw scores) were analyzed. RESULTS: At the time of the most recent examination, the obtained mean estimated FSIQ of 83.57 was more than one SD below expected population norms. A significant decline in cognitive performance during the time since XRT was demonstrated, with a mean loss of 2.55 estimated FSIQ points per year (P =.0001). An analysis for the basis of the intelligence quotient (IQ) loss revealed that subtest raw score values increased significantly over time since XRT, but the rate of increase was less than normally expected, which resulted in decreased IQ scores. CONCLUSION: These results support the hypothesis that MB patients demonstrate a decline in IQ values because of an inability to acquire new skills and information at a rate comparable to their healthy same-age peers, as opposed to a loss of previously acquired information and skills. (+info)
The effect of chelation therapy with succimer on neuropsychological development in children exposed to lead.
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BACKGROUND: Thousands of children, especially poor children living in deteriorated urban housing, are exposed to enough lead to produce cognitive impairment. It is not known whether treatment to reduce blood lead levels prevents or reduces such impairment. METHODS: We enrolled 780 children with blood lead levels of 20 to 44 microg per deciliter (1.0 to 2.1 micromol per liter) in a randomized, placebo-controlled, double-blind trial of up to three 26-day courses of treatment with succimer, a lead chelator that is administered orally. The children lived in deteriorating inner-city housing and were 12 to 33 months of age at enrollment; 77 percent were black, and 5 percent were Hispanic. Follow-up included tests of cognitive, motor, behavioral, and neuropsychological function over a period of 36 months. RESULTS: During the first six months of the trial, the mean blood lead level in the children given succimer was 4.5 microg per deciliter (0.2 micromol per liter) lower than the mean level in the children given placebo (95 percent confidence interval, 3.7 to 5.3 microg per deciliter [0.2 to 0.3 micromol per liter]). At 36 months of follow-up, the mean IQ score of children given succimer was 1 point lower than that of children given placebo, and the behavior of children given succimer was slightly worse as rated by a parent. However, the children given succimer scored slightly better on the Developmental Neuropsychological Assessment, a battery of tests designed to measure neuropsychological deficits thought to interfere with learning. All these differences were small, and none were statistically significant. CONCLUSIONS: Treatment with succimer lowered blood lead levels but did not improve scores on tests of cognition, behavior, or neuropsychological function in children with blood lead levels below 45 microg per deciliter. Since succimer is as effective as any lead chelator currently available, chelation therapy is not indicated for children with these blood lead levels. (+info)
Brain anatomy, gender and IQ in children and adolescents with fragile X syndrome.
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This study utilized MRI data to describe neuroanatomical morphology in children and adolescents with fragile X syndrome, the most common inherited cause of developmental disability. The syndrome provides a model for understanding how specific genetic factors can influence both neuroanatomy and cognitive capacity. Thirty-seven children and adolescents with fragile X syndrome received an MRI scan and cognitive testing. Scanning procedures and analytical strategies were identical to those reported in an earlier study of 85 typically developing children, permitting a comparison with a previously published template of normal brain development. Regression analyses indicated that there was a normative age-related decrease in grey matter and an increase in white matter. However, caudate and ventricular CSF volumes were significantly enlarged, and caudate volumes decreased with age. Rates of reduction of cortical grey matter were different for males and females. IQ scores were not significantly correlated with volumes of cortical and subcortical grey matter, and these relationships were statistically different from the correlational patterns observed in typically developing children. Children with fragile X syndrome exhibited several typical neurodevelopmental patterns. Aberrations in volumes of subcortical nuclei, gender differences in rates of cortical grey matter reduction and an absence of correlation between grey matter and cognitive performance provided indices of the deleterious effects of the fragile X mutation on the brain's structural organization. (+info)
Long-term quality of life and neuropsychologic functioning for patients with CNS germ-cell tumors: from the First International CNS Germ-Cell Tumor Study.
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This study evaluated the quality of life and neuropsychologic functioning among patients enrolled between 1989 and 1993 in the First International CNS Germ-Cell Tumor Study. Quality-of-life questionnaires (Short Form-36 or Child Health Questionnaire) were completed on 43 patients at median follow-up of 6.1 years after diagnosis (range, 4.5-8.8 years), and intellectual and academic testing was performed on 22 patients. Psychosocial and physical functioning of patients aged 19 years and older at follow-up was within the average range, whereas the same functioning for patients aged 18 years and younger, as reported by their parents at follow-up, was low average and borderline, respectively. Overall psychosocial and physical health summary scores were positively correlated with age at diagnosis for both groups combined. Those who received CNS radiation therapy (n = 29) reported significantly worse physical health, but similar psychosocial health, compared with those treated without radiation. Neuropsychologic testing indicated full-scale and verbal IQ, reading, spelling, and math skills in the average range, and performance IQ in the low average range. Intelligence and math skills were positively correlated with age at diagnosis. Those with germinomas significantly outperformed those with nongerminomatous/ mixed tumors on all neuropsychological measures administered. Younger patients diagnosed with CNS germ-cell tumors are at increased risk for psychosocial and physical problems as well as neuropsychologic deficits. Exposure to irradiation adversely affects overall physical functioning, whereas tumor pathology appears to be a salient neurocognitive risk factor. Collaborative and randomized studies are required to further elucidate the late effects arising from factors such as age at diagnosis, tumor histology, level of irradiation therapy, and chemotherapy toxicity among these young and potentially curable patients. (+info)
Functional genomics of the Down syndrome.
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Down syndrome, as a phenotypic result of trisomy 21, is a complex condition with a set of over 30 phenotypic features, which manifest themselves with varying frequencies among affected individuals. The importance for molecular medicine of understanding the molecular mechanisms underlying Down syndrome becomes fully appreciated when a striking feature of Down syndrome is taken into account: that the overdose of otherwise perfectly normal genes causes disorders of human health, indistinguishable from major public health problems of the general population, such as mandatory early onset Alzheimer s degeneration, increased risk of leukemia, and protection from cancer of solid tissues. The DNA sequence of human chromosome 21 is, at the moment, the most complete piece of DNA sequence known in the whole of human genome. The challenge for the future is an integrated, multidisciplinary approach to the molecular biology of chromosome 21 genes, in conjunction with the research into the variation in their genotype, expression, and function in the normal population, in Down syndrome individuals with well-characterized phenotypic traits, and in euploid patients suffering from diseases associated with phenotypic components of Down syndrome: mental retardation, developmental defects, hematological and solid tissue malignancies, and Alzheimer s disease. (+info)
Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children's Cancer Group study.
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PURPOSE: To investigate the intellectual outcomes of children with medulloblastomas/primitive neuroectodermal tumors (MB/PNET) treated with reduced-dose craniospinal radiotherapy (RT) plus adjuvant chemotherapy. PATIENTS AND METHODS: Forty-three children with average-risk posterior fossa MB/PNETs underwent longitudinal intelligence testing. All had been treated with a reduced-dose craniospinal RT regimen (23.4 Gy to the neuraxis, 32.4-Gy boost to the posterior fossa) and adjuvant chemotherapy. RESULTS: The estimated rate of change from baseline was significant for Full Scale Intelligence Quotient (FSIQ), Verbal IQ (VIQ), and Nonverbal IQ (NVIQ) (P <.001 for all three outcomes). The rate of change was estimated to be -4.3 FSIQ points per year, -4.2 VIQ points per year, and -4.0 NVIQ points per year. Females were more subject to VIQ decline than were males (P =.008), and young children (< 7 years of age) were more negatively affected than were older children, with a significant decline in NVIQ (P =.016). Finally, patients with higher baseline evaluations suffered greater declines in IQ than did those with lower baseline scores. CONCLUSION: This study represents the largest series of patients with average-risk MB/PNETs treated with a combination of reduced-dose RT and adjuvant chemotherapy whose intellectual development has been followed prospectively. Intellectual loss was substantial but suggestive of some degree of intellectual preservation compared with effects associated with conventional RT doses. However, this conclusion remains provisional, pending further research. (+info)
Effects of home environment, socioeconomic status, and health status on cognitive functioning in children with HIV-1 infection.
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OBJECTIVE: To investigate the effects of the home environment, socioeconomic status (SES), and health status on cognitive functioning in a sample of children with HIV-1 infection in a cross-sectional study. METHODS: Forty-three caregivers and their children (2.5 to 12 years) participated. Caregivers completed two self-report measures of the home environment that included questions regarding the organization of the environment, play materials, parental involvement, variety of stimulation, and parental attitudes toward the provision of a cognitively stimulating environment. Cognitive functioning was assessed using a standardized intelligence (IQ) test. Children's medical charts were reviewed for HIV-1 classification status (CDC, 1994), CD4 cell counts, and current medication. RESULTS: This study revealed two primary findings. First, measures of the home environment mediated the association between SES and child IQ. Second, measures of the home environment had a stronger association with child IQ during the advanced stages of disease than earlier stages of disease. CONCLUSIONS: The home environment is associated with cognitive functioning among children with HIV-1 infection. Moreover, interventions aimed at enhancing the quality of the home environment may have a positive impact on these children's cognitive development. (+info)
Influence of variation in birth weight within normal range and within sibships on IQ at age 7 years: cohort study.
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OBJECTIVE: To examine the relation between birth weight and measured intelligence at age 7 years in children within the normal range of birth weight and in siblings. DESIGN: Cohort study of siblings of the same sex. SETTING: 12 cities in the United States. SUBJECTS: 3484 children of 1683 mothers in a birth cohort study during the years 1959 through 1966. The sample was restricted to children born at >/=37 weeks gestation and with birth weights of 1500-3999 g. MAIN OUTCOME MEASURE: Full scale IQ at age 7 years. RESULTS: Mean IQ increased monotonically with birth weight in both sexes across the range of birth weight in a linear regression analysis of one randomly selected sibling per family (n= 1683) with adjustment for maternal age, race, education, socioeconomic status, and birth order. Within same sex sibling pairs, differences in birth weight were directly associated with differences in IQ in boys (812 pairs, predicted IQ difference per 100 g change in birth weight =0.50, 95% confidence interval 0.28 to 0.71) but not girls (871 pairs, 0.10, -0.09 to 0.30). The effect in boys remained after differences in birth order, maternal smoking, and head circumference were adjusted for and in an analysis restricted to children with birth weight >/= 2500 g. CONCLUSION: The increase in childhood IQ with birth weight continues well into the normal birth weight range. For boys this relation holds within same sex sibships and therefore cannot be explained by confounding from family social environment. (+info)