Neuropsychologic functioning of survivors of childhood medulloblastoma randomized to receive conventional or reduced-dose craniospinal irradiation: a Pediatric Oncology Group study.

PURPOSE: The purpose of this study was to test the hypothesis that survivors of medulloblastoma who were younger at diagnosis and those who received standard-dose cranial irradiation (SRT) of 36 Gy would have a lower performance on standardized tests of cognitive function and achievement than children who were older and those treated with reduced-dose cranial irradiation (RRT) of 23.4 Gy. PATIENTS AND METHODS: Eligible patients had been treated on Pediatric Oncology Group (POG) study 8631 for low-risk medulloblastoma that randomized patients to receive RRT or SRT after surgical resection. Those who were alive and free of progressive disease 6.1 to 9.9 years from completion of treatment were eligible for this study. Of the 35 eligible patients, 22 patients (13 SRT, nine RRT) participated in a battery of tests that included intellectual and academic development as well as ratings of health-related quality of life. RESULTS: Patients were stratified by treatment group (SRT v RRT) and into younger (Y) and older (O) groups by the median age at diagnosis (8.85 years), which resulted in four groups that we hypothesized would show neuropsychologic test scores in the following order: Y/SRT less than Y/RRT less than O/SRT less than O/RRT. Evidence to support the hypothesized ordering of groups in terms of neuropsychologic toxicity was obtained with regard to Performance Intelligence Quotient (IQ), Full Scale IQ, Attention, Reading, and Arithmetic. CONCLUSION: Children treated for medulloblastoma experienced less severe neuropsychologic toxicity when treated with 23.4 Gy instead of 36 Gy cranial irradiation. Older children experienced less toxicity than children who were younger at the time of irradiation.

Acute and long-term neurodevelopmental outcomes in children following bone marrow transplantation.

Bone marrow transplantation offers a potential cure for a number of childhood cancers, sickle cell anemia, and stabilization of a deteriorating and debilitating process in a number of metabolic disorders and leukodystrophies. Depending upon the disease, treatment prior to BMT, and natural history of the disease, BMT may increase the risk of neuropsychological toxicity for children undergoing BMT, or may actually improve their long-term neurodevelopmental outlook. The role of factors such as pre-BMT therapy, age at time of treatment, presence or absence of total body irradiation, and toxicities associated with GVHD are presented for consideration. A developmental model for understanding the emergence of neurocognitive effects of BMT is reviewed, and strategies for intervention are considered.

The effects of HIV on cognitive and motor development in children born to HIV-seropositive women with no reported drug use: birth to 24 months.

OBJECTIVE: This study documents delays in the mental and motor functioning of infants perinatally infected with human immunodeficiency virus (HIV) while controlling for confounding effects of prenatal drug exposure, ethnicity, socioeconomic status, and maternal separation and death. METHODS: The cognitive and motor development of 126 infants born to nondrug-using, HIV-seropositive Haitian women was assessed at 3-month intervals through 24 months of age using the Bayley Scales of Infant Development. By 18 months of age, 28 of the infants were diagnosed as HIV-infected, and the 98 uninfected infants served as a control group. The infected and uninfected infants did not differ with respect to mean gestational age, birth weight, ethnicity, or rates of maternal separation and death. RESULTS: By 3 months of age, the mean mental and motor scores of the infected infants were significantly lower than those of the uninfected controls. Furthermore, the initial differences between the two groups increased over time, as many of the infected infants became increasingly delayed. Although the infected infants tended to perform more poorly than the uninfected infants, nearly one third of the infected infants exhibited relatively normal cognitive development and half demonstrated relatively normal motor development. CONCLUSIONS: Over the first 24 months of life, the mean rate of development of HIV-infected infants is significantly slower than that of noninfected infants born to seropositive mothers. This occurs even when the effects are not confounded with those of prenatal drug exposure.

Cognitive functioning and brain magnetic resonance imaging in children with sickle Cell disease. Neuropsychology Committee of the Cooperative Study of Sickle Cell Disease.

OBJECTIVE: Brain magnetic resonance imaging (MRI) and neuropsychological evaluations were conducted to determine whether neuroradiographic evidence of infarct in children with sickle cell disease between ages 6 and 12 years would result in impairment in cognitive and academic functioning. METHOD AND DESIGN: Children enrolled in the Cooperative Study of Sickle Cell Disease were evaluated with brain MRI and neuropsychological evaluation. Completed studies were obtained for 194 children, 135 with HbSS. MRIs were categorized according to the presence of T2-weighted, high-intensity images suggestive of infarct and were further categorized on the basis of a clinical history of cerebrovascular accident (CVA). An abnormal MRI but no clinical history of CVA was classified as a silent infarct. Neuropsychological evaluations included assessment of both global intellectual functioning and specific academic and neuropsychological functions. RESULTS: Central nervous system (CNS) abnormalities were identified on MRI in 17.9% of the children (22.2% of children homozygous for HbS), and a clinical history of CVA (N = 9, 4.6%) was identified in only children with HbSS disease. Subsequent analyses examined only children with HbSS. Children with a history of CVA performed significantly poorer than children with silent infarcts or no MRI abnormality on most neuropsychological evaluation measures. Children with silent infarcts on MRI performed significantly poorer than children with no MRI abnormality on tests of arithmetic, vocabulary, and visual motor speed and coordination. CONCLUSIONS: These results substantiate the importance of careful evaluation, educational planning, and medical intervention for CNS-related complications in children with sickle cell disease.

Preparing children for medical examinations: the importance of previous medical experience.

The relationship between past medical experience and children's response to preparation for medical examinations was investigated in 79 pediatric outpatients aged 3 to 12 years. Children were randomly assigned to one of five preparation conditions prior to receiving a medical examination and a throat culture: sensory information about the exam, training in coping skills (deep breathing and positive self-talk), combined sensory information and coping skills training, attention control, and no-treatment control. The results indicated that children with previous negative medical experiences demonstrated more behavioral distress during a throat culture examination that did children with previous positive or neutral medical experiences. In addition, the attention control condition appeared to increase the distress of children with previous negative medical experiences. Amount of past exposure to the specific medical procedure was not related to observed distress. The implications of these findings for the preparation of children for medical procedures are discussed.

Pain and fear ratings: clinical implications of age and gender differences.

The study investigated the relationships among children's self-report of anticipatory pain and fear, physiological measures of distress, and previous medical experience in 62 outpatients during allergy skin testing. Younger (aged 3-7 years) and older (aged 8-12 years) children reported similar amounts of pain and fear. Girls reported more pain than boys. Older children and boys provided differential pain and fear ratings compared with younger children and girls. Younger children's self-report of distress was not related to any physiological measures, but older children's report of fear was significantly related to blood pressure. In girls, positive medical experience was correlated with less pain. The implications of these findings for the clinical measurement and intervention of children's distress during painful medical procedures are discussed.

A firearm safety program for children: they just can't say no.

The purpose of this study was to compare children's play and aggressive behavior with firearms before and after an information-based intervention. Correlates of aggression and gun play were also analyzed. Subjects were 24 pairs of preschool children videotaped for 10 minutes in a structured play setting, in which they had access to a variety of toys and to real and toy guns. One child from each dyad was then exposed to an information-based intervention and told not to play with guns. The children were again videotaped in the same setting approximately 1 week later. Results indicated that the intervention was ineffective in modifying the behavior of the children. Regression analyses revealed that access to a parent's firearm was correlated with gun play and that gun play and handling of firearms in the home were correlated with aggressive behavior. The findings in this study represent the first systematic attempt to decrease gun play in children and suggest that information provision alone is an insufficient intervention.

Coping and communication among parents and children with human immunodeficiency virus and cancer.

Coping strategies and communication of three groups of 20 preschool children and their parents were compared. One group was composed of children infected with the human immunodeficiency virus (HIV) who displayed clinical symptoms of the disease; the second group was composed of children diagnosed with cancer; and the third group was composed of healthy children. Results indicated that the parents of children with life-threatening illnesses reported greater degrees of wishful thinking than did control subjects. Furthermore, parents of children with HIV reported more wishful thinking than did parents of children with cancer. Finally, significantly more children with cancer were aware of their diagnosis than were children with HIV. The findings in this study suggest coping and communication difficulties for parents and children with HIV.

Behavioral management of children's distress during chemotherapy.

Three children, aged 11-14, undergoing cancer chemotherapy were coached in cue-controlled muscle relaxation, controlled breathing, pleasant imagery and positive self-talk during chemotherapy venopunctures. Using a multiple baseline across subjects design, 46-68% reductions from baseline levels of observed behavioral distress during venopunctures were found during intervention. Medical personnel and self-report ratings of the children's distress during venopunctures also decreased during intervention. Parental ratings of children's distress, however, did not change. Methodological issues in inpatient treatment of cancer patients and the self-report assessment of children's distress are discussed.

Neurocognitive aspects of pediatric sickle cell disease.

Studies pertaining to the neurocognitive functioning and learning of children in whom sickle cell disease is diagnosed are reviewed, and findings suggest diffuse neurocognitive deficits, with much variability across subjects. A hypothesis is presented about the cumulative nature of such deficits in children who have not sustained cerebral vascular accidents. Important methodological shortcomings in the literature are identified and recommendations are made for future neurocognitive research with children in whom sickle cell disease has been diagnosed. Studies pertaining to the psychosocial development of these children are also reviewed, and it is concluded that behavioral problems, low self-esteem, and disturbances of body image are frequently characteristic of these children. Recommendations are made including early special education and psychosocial intervention programs for children with sickle cell disease.

Pediatric HIV infection: a neuropsychological and educational challenge.

Pediatric acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection will soon be the primary infectious cause of perinatally acquired developmental disabilities in the United States. HIV encephalopathy and a variety of opportunistic infections, neoplasms, and vascular changes associated with pediatric HIV infection create a high probability of neuropsychological impairment among preschool and school-age children infected perinatally. Although the use of antiretrovirals may moderate some of the functional difficulties faced by these children, specific neuropathological and neuropsychological deficits are likely to remain. Treatments that prevent the central nervous system (CNS) effects of HIV have yet to be identified. As the epidemic progresses among women of child-bearing age, well-controlled developmental studies are needed to further clarify the relationship between HIV and child development, and to aid professionals in developing appropriate, school-based educational plans.

Hospitalizations for painful episodes: association with school absenteeism and academic performance in children and adolescents with sickle cell anemia.

Painful episodes have been identified as one of the most frequent manifestations of sickle cell anemia (hemoglobin HbSS). This retrospective study compared the frequency of hospitalization and the academic performance of two groups of children with HbSS (ages 8 to 18 years) with differing frequencies of pain. A high frequency (HF) group (n = 10) was composed of children who had four or more hospitalizations for pain in the study period; those in the low frequency (LF) group (n = 11) had one or no hospitalizations for pain during the study period. The two groups were matched on age (within 6 months), gender, and ethnicity. Standardized assessments of academic achievement and school records of attendance and class grades were obtained for all participants. The standardized academic achievement for both groups was approximately one standard deviation below the normative mean of the population sample, and class grades were below a C average. School absence was frequent in both groups (LF mean = 16.8 days/year; HF mean = 35.4 days/year), and children in the HF group had significantly more absences than children in the LF group. The lack of difference in academic performance between the two groups suggests that there may be factors other than school absenteeism that affect academic achievement, which require further investigation.

Neuroimaging abnormalities in adults with sickle cell anemia: associations with cognition.

OBJECTIVE: This study was conducted to determine the relationship of frontal lobe cortical thickness and basal ganglia volumes to measures of cognition in adults with sickle cell anemia (SCA). METHODS: Participants included 120 adults with SCA with no history of neurologic dysfunction and 33 healthy controls (HCs). Participants were enrolled at 12 medical center sites, and raters were blinded to diagnostic group. We hypothesized that individuals with SCA would exhibit reductions in frontal lobe cortex thickness and reduced basal ganglia and thalamus volumes compared with HCs and that these structural brain abnormalities would be associated with measures of cognitive functioning (Wechsler Adult Intelligence Scale, 3rd edition). RESULTS: After adjusting for age, sex, education level, and intracranial volume, participants with SCA exhibited thinner frontal lobe cortex (t = -2.99, p = 0.003) and reduced basal ganglia and thalamus volumes compared with HCs (t = -3.95, p < 0.001). Reduced volume of the basal ganglia and thalamus was significantly associated with lower Performance IQ (model estimate = 3.75, p = 0.004) as well as lower Perceptual Organization (model estimate = 1.44, p = 0.007) and Working Memory scores (model estimate = 1.37, p = 0.015). Frontal lobe cortex thickness was not significantly associated with any cognitive measures. CONCLUSIONS: Our findings suggest that basal ganglia and thalamus abnormalities may represent a particularly salient contributor to cognitive dysfunction in adults with SCA.

Differential medication of child versus adult postoperative patients: the effect of nurses' assumptions.

We examined nurses' assumptions concerning children and analgesia that have been hypothesized to explain the differential medication of postoperative child and adult patients. One hundred fourteen nurses from various pediatric and adult inpatient units of a large, urban teaching hospital were included in the study. A questionnaire consisting of four vignettes describing two hypothetical postoperative situations involving a child and adult patient, questions concerning choice of analgesic and assessment of pain for the hypothetical patients, and questions concerning the nurses' assumptions about children and analgesia was distributed to each nurse. The findings illustrate a pattern of differential medication of hypothetical child relative to hypothetical adult postoperative patients. The belief that children feel less pain than adults and concern about respiratory depression were associated with nurses' analgesia decisions.

Effects of maternal distraction versus reassurance on children's reactions to injections.

Manipulated experimentally mothers' verbal behavior during a routine intramuscular injection in order to help clarify the role of nonprocedural talk (distraction) and parental reassurance on children's reaction to the injection. 42 child-mother dyads were recruited from a general pediatric primary care clinic and were randomly assigned to a parental reassurance, parental nonprocedural talk (distraction) or minimal-treatment control group. Children in the maternal distraction condition exhibited significantly less distress during the immunization injection than those in the reassurance and control conditions. Specifically, children in the maternal distraction group exhibited less crying than children in the other two groups. Children in the reassurance and control groups did not differ from each other in terms of behavioral distress. The present findings serve further to bolster the evidence for the efficacy of maternal distraction as a way to ameliorate child distress during invasive medical procedures.

Impact of children's sickle cell history on nurse and physician ratings of pain and medication decisions.

The process of assessing and treating recurrent and unpredictable pain in children with sickle cell disease (SCD) is complex. A conceptual model is presented to aid in understanding the influence of mediating factors such as professional knowledge, attitudes and beliefs about pain, and learning history on the interpretation of objective data and resulting treatment decision. One aspect of this model, the effect of disease history on pain assessment and treatment decisions, is tested in an experimental study of SCD pain in children. Results suggest that nurses, but not pediatric residents, provide lower doses of narcotic analgesics to children with histories of frequent, as opposed to occasional, hospitalization for pain, although they do not differ in their ratings of the pain of children with these histories. Neither professional experience and training nor reported attitudes and beliefs about pain in children are related to this pattern of decision making. Results are discussed in terms of the aversive impact of repeated exposure to a noxious stimulus (pain behaviors) on caregiver interpretation of pain cues.

Interpersonal distance and coping in children with HIV and cancer.

We compared interpersonal distance and coping among two groups of pre-school pediatric patients diagnosed with either HIV or cancer and a third group of healthy children. In comparison to the children with cancer, children with HIV indicated greater mother-child interpersonal distance--a finding that correlated with mothers' reports of social withdrawal. Other notable findings included increased father-child distance in the HIV population and mother-child discrepancies of perceived interpersonal distance. In addition, seven of the children with HIV indicated that the adults turn away--a finding that correlated with the children's knowledge of their illness. We also explored the possible role of protective communication in the pediatric HIV population.

Enhanced parenting knowledge and skills in mothers of preschool children with sickle cell disease.

Compared 25 preschool children with sickle cell disease (SCD) to demographically matched healthy comparison children on maternal reports of child-rearing beliefs and practices and maternal and child behaviors related to social adjustment. Mothers of children with SCD possessed significantly more knowledge of appropriate discipline techniques. The groups did not differ on maternal reports of socially relevant child behavior. However, when mother-child interactions were observed in free play and structured play settings, mothers of children with SCD treated their children as competent significantly more, and treated their children as incompetent significantly less, than comparison mothers. Mothers of children with SCD also used significantly more reinforcement during the final toy pick-up condition. There were no observed differences between groups in the children's behavior.

Effects of parent presence on children's reactions to injections: behavioral, physiological, and subjective aspects.

Observed 47 children ranging in age from 13 months to 7 years 9 months receiving injections as part of a regular visit to a pediatric clinic. Twenty-three children were randomly assigned to a condition with parent (mainly mothers) present and 24 to a condition with parent absent. During the medical procedure, the child's reactions were observed via videotape (for later behavioral coding) and physiological recording (to measure heart rates). Following the injection, data were collected on the child's preference of condition (either parent present or parent absent) for future injections. Older children (but not younger ones) showed significantly more behavioral distress when the parent was present. However, the oldest children's preference of condition for future injections was overwhelmingly that of parent present (86%).

Neuropsychologic performance in school-aged children with sickle cell disease: a report from the Cooperative Study of Sickle Cell Disease.

OBJECTIVES: To compare the results of serial neuropsychologic testing in children with sickle cell disease with the results of serial magnetic resonance imaging (MRI) examinations, particularly to evaluate neuropsychologic function in the absence of overt stroke. STUDY DESIGN: In the Cooperative Study of Sickle Cell Disease, serial neuropsychologic and MRI tests were performed in 373 patients (255 with hemoglobin SS and 118 with hemoglobin SC), 6 to 18 years of age. MRI of the brain and a neuropsychologic battery that included the Wechsler Intelligence Scale for Children (WISC-R or WISC-III) and the Woodcock-Johnson Math and Reading Achievement Tests were performed concurrently and repeated every 2 to 3 years. A silent infarct was defined as an MRI finding of increased signal intensity on T(2) imaging in a patient without a history of stroke. RESULTS: Twenty-seven patients, all with hemoglobin SS, had overt strokes and 62 had silent infarcts (52 with hemoglobin SS). Patients with hemoglobin SS and silent infarcts had significantly lower scores for math and reading achievement, Full-Scale IQ, Verbal IQ, and Performance IQ, when compared with those with normal MRI findings. In children with hemoglobin SS and normal MRI findings, the scores for Verbal IQ, math achievement, and coding (a subscale of Performance IQ) declined with increasing age. CONCLUSIONS: School-aged children with sickle cell disease had compromised neuropsychologic function in the presence of silent infarcts. In addition, they had declines in performance in certain areas of function over time. Therapeutic interventions that prevent or lessen cognitive impairment are needed before school entry for children with sickle cell disease.