Celiane Rey-Casserly

Late effects of therapy for pediatric brain tumor survivors.

Approximately 2 of every 3 of all pediatric patients with brain tumors will be long-term survivors. However, there is a steep cost for pediatric brain tumor survivors, and the group as a whole faces significantly more late effects than many other survivors of pediatric cancers. Most of these effects can be attributed to direct neurologic damage to the developing brain caused by the tumor and its removal, the long-term toxicity of chemotherapy, or the effects of irradiation on the central nervous system. The late effects experienced by childhood brain tumor survivors involve multiple domains. This article will review the significant late effects that occur within the medical, neurocognitive, psychosocial, and economic domains of the survivorship experience. We conclude by discussing how the late effects in different domains often coexist and can create a complex set of obstacles that pose significant challenges for a survivor of a pediatric brain tumor on a daily basis.

Extremely preterm birth outcome: a review of four decades of cognitive research.

Premature birth incidence and survival rates are increasing steadily due to advances in obstetric and neonatal intensive care. Those born at the limits of viability are highly at-risk of adverse neurocognitive function over their lifespan, leading to current controversy regarding aggressive resuscitation efforts for these extremely preterm children. However, data from earlier generation cohorts who were born in substantially different eras of neonatal intensive care cannot be relied on to predict outcome of today’s newborn. Our review by the crucial variable of birth cohort year shows a changing developmental trajectory in which today’s extremely preterm survivor is likely to have fewer severe medical complications, better neurological outcomes, and fewer adverse cognitive late effects. Such data further underscore the importance of concurrently considering medical, familial, socioenvironmental, and neurobiological factors in combination with individual neonatal intensive care center protocols when studying outcomes of the preterm child. This complex, interrelated range of factors directly affects the immature, rapidly developing premature brain. However, ongoing surveillance to detect subsequent delay or impairment and to apply interventional strategies early in the developmental course holds promise for further enhancement of functional outcome.

Medical, psychological, cognitive and educational late-effects in pediatric low-grade glioma survivors treated with surgery only†

Surgical resection is often the only treatment necessary for pediatric low‐grade gliomas (LGGs) and is thought to define a population with an excellent long‐term prognosis. The goal of this study was to describe the multidimensional late‐effects of pediatric LGG survivors treated exclusively with surgery.

DEVELOPMENTAL PERSPECTIVES ON OPTIMIZING EDUCATIONAL AND VOCATIONAL OUTCOMES IN CHILD AND ADULT SURVIVORS OF CANCER

Over the last few decades, long-term survival rates of children diagnosed with the two most common forms of childhood cancer, acute lymphoblastic leukemia (ALL) and brain tumors have improved substantially. Neurodevelopmental and psychosocial sequelae resulting from these diseases and their treatment have a direct impact on the developing brain and on the quality of life of these children and their families. The focus of this article is on optimizing neuropsychological and adaptive outcomes for children who have been successfully treated for these cancers and whose prospects for long-term survival are increasingly encouraging. We present a model for understanding systemic interactions among the multiple factors that influence the childs development over time and take into account contextual variables. Strategies for optimizing cognitive and psychosocial outcomes or ameliorating late effects need to consider treatment histories, specific stages of development, the contextual demands/developmental challenges associated with each, and the resources (internal and external to the child) available to meet these challenges. The challenges faced by survivors at the early childhood, middle childhood, adolescent, and emerging adulthood stages are discussed. We review different types of interventions and discuss how these can contribute to optimal functioning in survivors of childhood ALL and brain tumors.

Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1

Objective: To assess the efficacy of lovastatin on visuospatial learning and attention for treating cognitive and behavioral deficits in children with neurofibromatosis type 1 (NF1). Methods: A multicenter, international, randomized, double-blind, placebo-controlled trial was conducted between July 2009 and May 2014 as part of the NF Clinical Trials Consortium. Children with NF1 aged 8–15 years were screened for visuospatial learning or attention deficits (n = 272); 146 children demonstrated deficits at baseline and were randomly assigned to lovastatin (n = 74; 40 mg/d) or placebo (n = 70). Treatment was administered once daily for 16 weeks. Primary outcomes were total errors on the Cambridge Neuropsychological Test Automated Battery Paired Associate Learning task (visuospatial learning) and the Score subtest from the Test of Everyday Attention for Children (sustained attention). Secondary outcomes measured executive function, attention, visuospatial skills, behavior, and quality of life. Primary analyses were performed on the intention-to-treat population. Results: Lovastatin had no significant effect on primary outcomes after 16 weeks of treatment: visuospatial learning (Cohen d = −0.15, 95% confidence interval −0.47 to 0.18) or sustained attention (Cohen d = 0.19, 95% confidence interval −0.14 to 0.53). Lovastatin was well tolerated, with no increase in reported adverse events compared to placebo. Conclusions: Lovastatin administered once daily for 16 weeks did not improve visuospatial learning or attention in children with NF1 and is not recommended for amelioration of cognitive deficits in this population. ClinicalTrials.gov identifier: This study was registered at ClinicalTrials.gov (NCT00853580) and Australian New Zealand Clinical Trials Registry (ACTRN12607000560493). Classification of evidence: This study provides Class I evidence that for children with NF1, lovastatin does not improve visuospatial learning or attention deficits.

Pilot study of a novel computerized task to assess spatial learning in children and adolescents with neurofibromatosis type 1.

Difficulties with visual-spatial learning are frequently observed and often considered to be the hallmark of neurocognitive impairment in neurofibromatosis type 1. The computerized Arena Maze is a virtual environment task that has been developed as a human paradigm to the Morris Water Maze, which is used to evaluate spatial learning in animal models. The authors evaluated this task as a measure of spatial learning in children with neurofibromatosis type 1 compared with their unaffected siblings. Affected children were able to learn the task and navigate the virtual environment; however, they performed more poorly on standard measures of spatial learning and spatial working memory than their siblings. The group with neurofibromatosis type 1 demonstrated decreased proficiency in earlier target trials and had more difficulty in remembering target location. This study demonstrates the potential utility of a novel virtual task to assess spatial learning deficits in children with neurofibromatosis type 1.

Executive Function in Children with Attention Deficit/Hyperactivity Disorder: the NIH EXAMINER battery

Theories of attention deficit/hyperactivity disorder (ADHD) increasingly highlight the role of neuropsychological impairment in ADHD; however, a consistent and identifiable pattern of performance on tests is not well established. The National Institutes of Health (NIH) Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) battery provides measures of common variance across multiple executive function tests within specific domains and was used to characterize which executive functions are most affected in children with ADHD. Thirty-two children (24 male), ages 8-15 years (M = 12.02; SD = 2.29), diagnosed with ADHD and no comorbid disorder completed the NIH EXAMINER battery. Sixty age and gender matched healthy controls were chosen from a database of participants enrolled in the NIH EXAMINER multi-site study. Children with ADHD performed worse on the working memory score compared with the controls. No differences were found on the cognitive control or fluency scores. For children with ADHD, poorer working memory performance predicted parent report of child learning problems. Cognitive control and fluency scores did not predict learning problems. In summary, working memory emerges as a primary impairment in children with ADHD who have no comorbid disorders. Furthermore, working memory weaknesses may underlie the academic problems often seen in children with ADHD.

Supervision in Neuropsychological Assessment: A Survey of Training, Practices, and Perspectives of Supervisors

Within the psychology supervision literature, most theoretical models and practices pertain to general clinical or counseling psychology. Supervision specific to clinical neuropsychology has garnered little attention. This survey study explores supervision training, practices, and perspectives of neuropsychology supervisors. Practicing neuropsychologists were invited to participate in an online survey via listservs and email lists. Of 451 respondents, 382 provided supervision to students, interns, and/or fellows in settings such as VA medical centers (37%), university medical centers (35%), and private practice (15%). Most supervisors (84%) reported supervision was discussed in graduate school “minimally” or “not at all.” Although 67% completed informal didactics or received continuing education in supervision, only 27% reported receiving training specific to neuropsychology supervision. Notably, only 39% were satisfied with their training in providing supervision and 77% indicated they would likely participate in training in providing supervision, if available at professional conferences. Results indicate that clinical neuropsychology as a specialty has paid scant attention to developing supervision models and explicit training in supervision skills. We recommend that the specialty develop models of supervision for neuropsychological practice, supervision standards and competencies, training methods in provision of supervision, and benchmark measures for supervision competencies.

Know thyself: real-world behavioral correlates of self-appraisal accuracy.

Accurate appraisal of ones own abilities is one metacognitive skill considered to be an important factor affecting learning and behavior in childhood. The present study measured self-appraisal accuracy in children using tasks of executive function, and investigated relations between self-appraisal and informant ratings of real-world behaviors measured by the BRIEF. We examined self-appraisal accuracy on fluency tasks in 91 children ages 10–17. More accurate self-appraisal was correlated with fewer informant ratings of real-world behavior problems in inhibition and shifting, independent of actual performance. Findings suggest that self-appraisal represents cognitive processes that are at least partially independent of other functions putatively dependent on the frontal lobes, and these self-appraisal-specific processes have unique implications for optimal daily function.

Focal brain dysfunction in a 41-year old man with familial alternating hemiplegia

The acute pathophysiologic changes during hemiplegic spells and the long-term outcome of alternating hemiplegia remain obscure. In a 41-year-old male with familial alternating hemiplegia we found an increase in right frontal cerebral blood flow 3 h into a 5-h left hemiplegic episode. A repeat high-resolution brain SPECT study performed 26 h after the resolution of the left hemiplegia revealed normalization of the frontal blood flow accompanied by hyperperfusion in the right parietal lobe. An interictal SPECT scan several weeks later showed no asymmetries. Head CT and MRI scans were negative. Neuropsychologic assessment and neurologic examination revealed evidence of a diffuse disorder which predominantly involved the right hemisphere. To our knowledge, there are no previous correlative studies of serial highresolution brain SPECT with MRI, or of detailed neuropsychologic assessment, in adult patients with such an advanced course of alternating hemiplegia of childhood.