Cognitive and adaptive functioning after liver transplantation for maple syrup urine disease: a case series.

MSUD is a complex metabolic disorder that has been associated with central nervous system damage, developmental delays, and neurocognitive deficits. Although liver transplantation provides a metabolic cure for MSUD, changes in cognitive and adaptive functioning following transplantation have not been investigated. In this report, we present data from 14 patients who completed cognitive and adaptive functioning testing pre- and one yr and/or three yr post-liver transplantation. Findings show either no significant change (n=8) or improvement (n=5) in IQ scores pre- to post-liver transplantation. Greater variability was observed in adaptive functioning scores, but the majority of patients evidenced no significant change (n=8) in adaptive scores. In general, findings indicate that liver transplantation minimizes the likelihood of additional central nervous system damage, providing an opportunity for possible stabilization or improvement in neurocognitive functioning.

Friendships and social interactions of school-aged children with migraine.

We set out to evaluate the friendships and social behaviour of school-aged children with migraine. Concern exists regarding the impact of paediatric migraine on daily activities and quality of life. We hypothesized that children with migraine would have fewer friends and be identified as more socially sensitive and isolated than comparison peers. Sixty-nine children with migraine participated in a school-based study of social functioning. A comparison sample without migraine included classmates matched for gender, race and age. Children with migraine had fewer friends at school; however, this effect was limited to those in elementary school. Behavioural difficulties were not found. Middle-school students with migraine were identified by peers as displaying higher levels of leadership and popularity than comparison peers. Concern may be warranted about the social functioning of pre-adolescent children with migraine; however, older children with migraine may function as well as or better than their peers.

Staged informed consent for a randomized clinical trial in childhood leukemia: impact on the consent process.

BACKGROUND: Children Cancer Group (CCG) 1991 is the first childhood acute lymphoblastic leukemia trial within CCG that allowed the utilization of a staged approach to the consent process. METHODS: One hundred and forty subjects participated in the Project on Informed Consent which compared the primary outcome measures in the consent process of patients enrolled in CCG-1991 with those enrolled in other CCG leukemia studies. RESULTS: The parents' trust scores were higher for the CCG-1991 compared with other protocols. Eighty percent of parents enrolled in CCG-1991 understood the distinction between the randomized clinical trial and the standard treatment arm, compared with 62.5% in the other studies, P = 0.05. Multiple other outcome measures suggested a positive impact from staged informed consent. CONCLUSIONS: Our results suggest that a consent process with a staged approach can help investigators obtain a more truly informed consent. Future research is needed to confirm the benefits of the staged approach to the informed consent process.

Sibling adjustment to pediatric traumatic brain injury: a case-controlled pilot study.

OBJECTIVE: To assess depressive symptoms, self-concept, and behavior in non-affected siblings of children with severe pediatric traumatic brain injury (TBI). DESIGN: Cross-sectional study with case controls. SETTING: Children's hospital tertiary care center. PARTICIPANTS: Twelve siblings of children consecutively admitted to an inpatient rehabilitation unit after a severe TBI. Case controls were randomly selected from the sibling's classmates. MAIN OUTCOME MEASURES: The Child Behavior Checklist (CBCL), the Teacher's Report Form of the CBCL (TRF-CBCL), the Self-Perception Profile for Children and the Children's Depression Inventory (CDI). RESULTS: No statistical differences were found in depressive symptoms, self-concept, or behavior between the siblings and their classmates 3 to 18 months after injury. Poorer functional outcomes in the child with a TBI were found to correlate significantly with lower self-concept and more symptoms of depression in the siblings. CONCLUSIONS: Further research is needed to evaluate the potential impact on sibling adjustment after pediatric TBI.

Neuropsychological functioning of youths with sickle cell disease: comparison with non-chronically ill peers.

OBJECTIVE: To compare the neuropsychological functioning of children with sickle cell disease (SCD) with no evidence of overt clinical stroke to that of classmates without a chronic illness matched on gender, race, and age. We examined both overall level of performance and patterns of performance utilizing empirically derived construct scores of key domains of neurocognitive functioning. METHODS: An abbreviated neuropsychological battery of tests was given to 31 children with SCD and 31 case controls. Empirically derived construct scores were developed for primary analyses. RESULTS: Children with SCD had significantly lower scores on three level-of-performance construct scores: total, verbal, and attention/memory. Mean scores for children with SCD were lower than those for case controls on every level-of-performance construct score and every standardized test score. However, pattern-of-performance construct scores were not significantly different. CONCLUSIONS: Children with SCD without overt stroke demonstrate significant deficits in neurocognitive functioning compared to classroom case controls. These findings highlight the impact of SCD on general neurocognitive functioning and suggest that routine screening of cognitive functioning should be a requisite element of comprehensive care for children with SCD. Within the context of documented physical limitations, we conclude that children with SCD are at very high risk for impaired psychosocial outcomes.

Aggression, antisocial behavior, and substance abuse in survivors of pediatric cancer: possible protective effects of cancer and its treatment.

OBJECTIVE: To examine aggression, antisocial behavior, and substance abuse in young adult survivors of pediatric cancer (PCS) relative to case control peers (CC). METHODS: We obtained self-reports of current aggression, antisocial behavior, and lifetime substance use from 26 PCS (time off-treatment, M: = 56 months) and 26 CC using the Antisocial Behavior Checklist and the Drinking and Drug History. A report of current aggression and antisocial behavior also was obtained from primary caregivers using the Child Behavior Checklist. RESULTS: PCS self-reported significantly less illegal drug use and experimentation than CC. No significant differences emerged between groups for use of alcohol and tobacco nor for aggression and antisocial behavior. CONCLUSIONS: PCS are functioning as well as, or better than, CC in terms of aggression, antisocial behavior, and substance abuse. However, given the compromised health status of survivors, efforts should focus on further reduction of drug-related risk behaviors that may amplify organ damage or increase risk for further malignancies in this population.

Social, emotional, and behavioral functioning of children with juvenile rheumatoid arthritis.

OBJECTIVE: To investigate the hypothesis that children with juvenile rheumatoid arthritis (JRA) would have more social and emotional problems than case-control classmates. METHODS: Using a case-control design, children with JRA (n = 74), ages 8-14, were compared with case-control classmates (n = 74). Peer relationships, emotional well-being, and behavior, based on peer-, teacher-, parent-, and self-report scores on common measures, were compared using analysis of variance. RESULTS: Relative to case-control classmates, children with JRA were similar on all measures of social functioning and behavior. Mothers reported more internalizing symptoms in the child with JRA, but child self reports and father reports showed no differences. Scores on all standardized measures were in the normal range for both the JRA and the case-control groups. CONCLUSION: Children with JRA were remarkably similar to case-control children on measures of social functioning, emotional well-being, and behavior. These findings are not supportive of disability/stress models of chronic illness in childhood and suggest considerable psychological hardiness among children with JRA.

Psychosocial adjustment of children with chronic illness: an evaluation of three models.

This study was designed to assess social, emotional, and behavioral functioning of children with chronic illness and to evaluate three models addressing the impact of chronic illness on psychosocial functioning: discrete disease, noncategorical, and mixed. Families of children with cancer, sickle cell disease, hemophilia, and juvenile rheumatoid arthritis participated, along with families of classroom comparison peers without a chronic illness who had the closest date of birth and were of the same race and gender (COMPs). Mothers, fathers, and children provided information regarding current functioning of the child with chronic illness or the COMP child. Child Behavior Checklist and Children's Depression Inventory scores were examined. Results provided support for the noncategorical model. Thus, the mixed model evaluated in this study requires modifications before its effectiveness as a classification system can be demonstrated.

Social, emotional, and behavioral functioning of children with cancer.

OBJECTIVE: It was hypothesized that children with cancer would have more social problems and difficulties with emotional well-being than case control, same race/gender, similarly aged classmates. STUDY DESIGN: Using a case controlled design, children with any type of cancer requiring chemotherapy except brain tumors (n = 76), currently receiving chemotherapy, ages 8 to 15, were compared with case control classroom peers (n = 76). Peer relationships, emotional well-being, and behavior were evaluated based on peer, teacher, parent, and self-report, and were compared using analysis of variance and structural equation modeling. RESULTS: Relative to case controls, children with cancer were perceived by teachers as being more sociable; by teachers and peers as being less aggressive; and by peers as having greater social acceptance. Measures of depression, anxiety, loneliness, and self-concept showed no significant differences, except children with cancer reported significantly lower satisfaction with current athletic competence. There were also no significant differences in mother or father perceptions of behavioral problems, emotional well-being, or social functioning. Scores on all standardized measures were in the normal range for both groups. Comparisons of the correlation matrices of children with cancer and to the correlation matrix of the comparison children using structural equation modeling suggested they were not significantly different. CONCLUSIONS: Children with cancer currently receiving chemotherapy were remarkably similar to case controls on measures of emotional well-being and better on several dimensions of social functioning. These findings are not supportive of disability/stress models of childhood chronic illness and suggest considerable psychologic hardiness.

A controlled study of peer relationships of children surviving brain tumors: teacher, peer, and self ratings.

OBJECTIVE: Evaluate the behavioral reputation and peer acceptance of children diagnosed and treated for brain tumors. METHOD: Twenty-eight children surviving brain tumors (8-18 years of age) were compared to 28 nonchronically ill, same classroom, same gender comparison peers (COMP). Peer, teacher, and self-report data were collected. RESULTS: Relative to COMP, children who had been diagnosed with brain tumors received fewer friendship nominations from clasmates and were described by peer, teacher, and self-report as socially isolated. Although they were no longer receiving therapy for their disease, peers perceived brain tumor survivors as being sick, more fatigued, and often absent from school. CONCLUSIONS: These data suggest that children surviving brain tumors are at risk for social difficulties even after treatment ends, although the specific cause(s) for this vulnerability were not investigated in the current study.

Informed consent in the Childrens Cancer Group: results of preliminary research.

BACKGROUND: Informed consent is critical to the ethical conduct of pediatric cancer clinical research. Research regarding such consent has been limited. METHODS: After conducting a background survey of institutional practice from principal investigators (PIs) at 113 Childrens Cancer Group (CCG) centers, the authors obtained more detailed data regarding informed consent from 23 parents of children recently enrolled in CCG research trials and from 23 clinician-investigators at 5 CCG institutions. RESULTS: Approximately 73% of PIs responded to the background survey, providing context in which to interpret the more detailed information. Parents reported that they found the informed consent process helpful, although somewhat confusing. Satisfaction with informed consent was not related to ethnicity or education level. Parents found discussion with staff more helpful than the consent document, and the majority reported that the amount of information conveyed was appropriate. Although only 3 parents (13%) reported that too much information was given, nearly 50% of the investigators believed too much information usually is provided. All investigators believed that patients benefit from participation in CCG studies; the majority recommend that the child be enrolled on study, and the majority believe the major obstacle to good informed consent is parents' "state of shock." CONCLUSIONS: Parents expressed general satisfaction with the consent process. By contrast, clinician responses indicate dissatisfaction with the informed consent process. Future research must include more centers and larger numbers of parents of children who we enrolled as well as those who declined to participate in CCG studies, examine consent in minority subgroups, and further investigate the role of clinician-investigators and their interaction with parents and children during the informed consent process.

Social functioning of children surviving bone marrow transplantation.

OBJECTIVE: To evaluate the behavioral reputation and peer acceptance of pediatric bone marrow transplant (BMT) survivors. METHODS: Forty-eight BMT survivors (8-16 years of age) were compared to 48 nonchronically ill, same-classroom, same-gender comparison peers (COMP). Peer, teacher, and self-report data were collected. RESULTS: Relative to COMP, BMT survivors had fewer friends and were described by peers, but not teacher or self-report, as more socially isolated. In addition, peers described BMT survivors as being less physically attractive and athletically skilled. Further analyses suggested that these nonsocial attributes (physical appearance and athletic ability) and treatment variables (whether cranial irradiation was received) mediated the social difficulties of BMT survivors. CONCLUSIONS: These data are suggestive of an unremitting pattern of difficulties with peers that has the potential to disrupt normal social and emotional development. Differences between peer, teacher and self-reports highlight the need for multiple informants in future work.

Child-rearing practices of primary caregivers of children with sickle cell disease: the perspective of professionals and caregivers.

OBJECTIVE: To obtain caregiver and medical professional opinions regarding the child-rearing practices of caregivers of children with sickle cell diseases (SCD). METHODS: We obtained self-reports of parenting practices from 48 caregivers of children with SCD and 48 caregivers of matched classroom comparison peers using the Child-Rearing Practices Report (CRPR). CRPR ratings were also obtained from 12 experts in pediatric SCD regarding their predictions of how a parent of a child with SCD would respond. The experts predicted differences in protectiveness, discipline, and excessive worry. Objective interim and lifetime illness severity scores were obtained for the children with SCD. RESULTS: Caregivers showed similarity between the two groups, disagreement with the experts, and minimal relationship to illness severity. CONCLUSIONS: Experts who work with children with chronic illnesses such as SCD seem to have stereotyped ideas that do not correspond with parental reports of their child-rearing practices, suggesting the need for careful clinical evaluations.

Potential bias in classroom research: comparison of children with permission and those who do not receive permission to participate.

Compared both the social reputation and preference/acceptance of children who received (n = 4,073) and did not receive parental consent (n = 469) to participate in classroom-based sociometric research. Peers and teachers described nonparticipants as less sociable. Peers described nonparticipants as being lower on social acceptance, more aggressive, and less academically competent. No significant differences were obtained for sensitive/isolated characteristics, appearance, or athleticism. There were no significant interactions between consent status and sex or age. Associations between social reputation and social preference scores were similar for participants and nonparticipants. The findings suggest that children who do not return consent forms are systematically different from classmates who participate, although these differences were modest. Further work is needed to determine why children do not participate.

Behavioral adjustment and social functioning of long-term survivors of childhood leukemia: parent and teacher reports.

Obtained parent and teacher reports of behavior and social competence for children who were survivors of acute lymphoblastic leukemia (ALL). At follow-up, children were 5-18 years of age, 48 months postdiagnosis, in first continuous remission, and off chemotherapy. Each child had been randomized to receive either 1,800 cGy whole brain radiation therapy (WBRT) plus intrathecal methotrexate (IT MTX), or IT MTX alone as central nervous system prophylaxis, and one of four chemotherapy regimens that varied in treatment intensity. Scores on standardized measures (CBCL-P/T and PIC) were generally similar to instrument norms. Parents, but not teachers, reported heightened child somatic concerns. There was no effect of WBRT or chemotherapy regimen on ratings of behavioral adjustment. Results indicate minimal psychosocial morbidity among long-term survivors of ALL and suggest that the stressful life events associated with cancer and its treatment do not cause significant behavioral or emotional difficulties.

Peer relationships and emotional well-being of youngsters with sickle cell disease.

Comparisons with measures of peer relationships and emotional well-being were made between youngsters with sickle cell disease (SCD) and same-classroom comparison peers. Relative to the comparison subjects, females with SCD were perceived by peers as being less sociable and less well accepted; males with SCD were perceived as being less aggressive than comparison peers. For both males and females with SCD, no other differences were identified on numerous measures of emotional well-being. None of the multiple measures of illness severity were significantly related to measures of psychological adjustment. The common side effects of SCD, chronic fatigue and small physical size, may divert males with the illness from manifesting difficulties related to aggressive behavior with peers. For females with the illness, the common side effects of the illness may hinder the development of normal social relationships. Despite chronic exposure to numerous stressful life events associated with SCD, the youngsters with the illness were remarkably similar to comparison peers, showing evidence of considerable hardiness.

Pre- and post-stroke MRI and neuropsychological studies in sickle cell disease: a case study.

The case of a patient with sickle cell disease is presented in which neuropsychological and magnetic resonance imaging studies were completed prior to and after a right hemispheric stroke. The contribution of a new MR perfusion technique in understanding the neurological complications in this patient is discussed. This case illustrates the complex pathophysiology of neuropsychological deficits in SCD and underscores the need to develop models that better reflect this complexity.

Social competence of siblings of children with sickle cell anemia.

Examined the peer relationships of siblings of children with SCA (N = 37), comparing them to a matched group of classroom comparison children who were the same race/gender, closest date of birth. Social reputation was examined from the perspective of teacher and peers; peer ratings and nominations of social acceptance were obtained; and information was obtained about the sibling's own view of their peer relationships. No differences were found between the two groups, suggesting that the overall functioning of this group of siblings was comparable to peers in their classrooms. Findings are discussed in terms of professional biases, the lack of empirical data relevant to the issue of sibling competence, and resilience.

Neuropsychological effects of cranial irradiation in young children with acute lymphoblastic leukemia 9 months after diagnosis. The Children's Cancer Group.

STUDY OBJECTIVE: To determine the effects of cranial irradiation on neuropsychological test performance evident 9 months after diagnosis. DESIGN: A companion study to a randomized clinical trial (CCG-105). SETTING: Institutions participating in Childrens Cancer Group cooperative treatment trials. PATIENTS: Seventy-four children aged 3.0 to 6.5 years with average-risk acute lymphoblastic leukemia. Children with central nervous system leukemia at the time of diagnosis, preexisting mental retardation, or Down's syndrome or for whom English was not the primary language were not eligible for study. INTERVENTIONS: Children were randomized to receive treatment with one of four systemic chemotherapy regimens and either intrathecal methotrexate sodium during induction and consolidation plus 18 Gy of cranial irradiation or intrathecal methotrexate during induction, consolidation, and maintenance as central nervous system prophylaxis. MEASUREMENT AND RESULTS: The groups were comparable with regard to chronologic age, sex, and family socioeconomic status. Children who received cranial irradiation plus intrathecal methotrexate scored significantly lower on the McCarthy Motor Scale (P < .05) and the Token Test (P < .05) than children who received intrathecal methotrexate alone. The groups did not differ significantly on the McCarthy General Cognitive Index, Developmental Test of Visual Motor Integration, or Peabody Picture Vocabulary Test-Revised. CONCLUSIONS: Findings suggest that the combined effects of cranial irradiation and intrathecal methotrexate therapy on neuropsychological performance may be evident in young children as early as 9 months after diagnosis. Follow-up assessment of these children will reveal whether these effects remain constant, intensify, or resolve.

Long-term neurobehavioral outcome in pediatric brain-tumor patients: review and methodological critique.

This paper provides an overview of pediatric brain tumors and reviews the literature on long-term neurobehavioral outcomes for these children. Progress in this area has been slow due to numerous methodological and practical complications. While some general conclusions can be drawn, the development of comprehensive models awaits more research into the multiplicity of biological and nonbiological events, and their interactions, potentially affecting outcome. Increased theoretical and methodological sophistication will be needed to address this complex classification of diseases. Barriers to research in this area are enumerated as are suggestions for future efforts.