Working memory in survivors of childhood acute lymphocytic leukemia: functional neuroimaging analyses.

BACKGROUND: Research on the physical and psychological late effects of treatment of childhood cancer has led to the identification of significant long-term neurocognitive deficits experienced by some survivors, particularly in the areas of memory and executive functioning. Despite indications of deficits based on cognitive assessment, the identification of specific mechanisms of neurocognitive deficits using neuroimaging techniques has yet to be adequately considered. PROCEDURE: This study used functional neuroimaging techniques to examine working memory and executive functioning deficits of survivors of childhood acute lymphocytic leukemia (ALL), as compared to age- and gender-matched healthy controls. RESULTS: There was a trend for ALL survivors to perform more poorly on a working memory task in terms of overall accuracy. Additionally, survivors displayed significantly greater activation in areas underlying working memory (dorsolateral and ventrolateral prefrontal cortex) and error monitoring (dorsal and ventral anterior cingulate cortex). CONCLUSIONS: These results support the theory of compensatory activation in necessary brain regions in order to complete tasks in pediatric ALL survivors, similar to that observed in multiple sclerosis patients. Concurrent examination of testing and brain imaging enables the connection of behavioral observations with underlying neurological characteristics of deficits in survivors and may help provide insight into mechanisms through which deficits appear.

Executive function, coping, and behavior in survivors of childhood acute lymphocytic leukemia.

OBJECTIVE: To examine the role of executive function in coping and behavioral outcomes in childhood acute lymphocytic leukemia (ALL) survivors. METHODS: We examined associations among several domains of executive function (working memory, behavioral inhibition, cognitive flexibility, and self-monitoring), coping, and emotional/behavioral problems in 30 children and adolescents ages 10- to 20-years old who completed treatment for ALL and 30 healthy controls matched on age and sex. RESULTS: We found partial support for our hypothesis that performance on executive function measures is associated with strategies used to cope with stress, and emotional and behavioral problems in ALL survivors. CONCLUSIONS: Findings suggest that executive function impairment may be associated with difficulties in coping and emotion regulation in a subgroup of children treated for ALL. Directions for future research on executive function deficits and coping skills in survivors of pediatric ALL are suggested.

Poorly differentiated small-cell neuroendocrine carcinoma of the submandibular gland: a case report.

Neuroendocrine carcinoma (NEC) is uncommon in the head and neck and rare in the salivary glands. In the latter location, it may manifest as pain or a palpable mass. These tumors can be quite aggressive, with a tendency toward recurrence and regional and distant metastasis. Because of the limited number of reported cases in the literature, no reliable treatment has been established. We describe the case of a 79-year-old man who presented with a persistent submandibular mass that was suspicious for a malignancy on imaging. Following surgical resection and histopathologic analysis, a diagnosis of poorly differentiated small-cell NEC was made. The patient was further treated with postoperative chemotherapy, and he exhibited no evidence of recurrence or metastasis on follow-up.

Effect of propranolol on functional connectivity in autism spectrum disorder--a pilot study.

A decrease in interaction between brain regions is observed in individuals with autism spectrum disorder (ASD), which is believed to be related to restricted neural network access in ASD. Propranolol, a beta-adrenergic antagonist, has revealed benefit during performance of tasks involving flexibility of access to networks, a benefit also seen in ASD. Our goal was to determine the effect of propranolol on functional connectivity in ASD during a verbal decision making task as compared to nadolol, thereby accounting for the potential spurious fMRI effects due to peripheral hemodynamic effects of propranolol. Ten ASD subjects underwent fMRI scans after administration of placebo, propranolol or nadolol, while performing a phonological decision making task. Comparison of functional connectivity between pre-defined ROI-pairs revealed a significant increase with propranolol compared to nadolol, suggesting a potential imaging marker for the cognitive effects of propranolol in ASD.

A meta-analysis of the neurocognitive sequelae of treatment for childhood acute lymphocytic leukemia.

BACKGROUND: Impaired neurocognitive functioning is one increasingly recognized long-term consequence of childhood ALL treatment. However, research findings have been inconsistent regarding the domains affected and the degree to which they are compromised. PROCEDURE: A comprehensive meta-analytic review of the long-term neurocognitive effects of childhood ALL was conducted. Studies were included if they were published in English, reported original quantitative data on the post-treatment neurocognitive functioning of childhood ALL patients in first remission and control groups, and used neurocognitive measures with adequate psychometric properties and published normative data. RESULTS: Data from 28 empirical studies yielding 13 effect sizes across nine domains were extracted and analyzed. All effects were negative (g = -0.34 to -0.71), demonstrating that ALL survivors consistently experienced significant deficits in intellectual functioning, academic achievement, and specific neurocognitive abilities compared to control groups. The role of potential moderators, including treatment with cranial irradiation, age at time of diagnosis, and time since treatment ended, was examined. However, no effects emerged as clearly and consistently moderated by these variables. CONCLUSIONS: The results from this meta-analysis suggest that declines in both global and specific areas of areas of neurocognitive functioning occur as a result of contemporary ALL treatment. Such deficits have significant implications for survivors' academic achievement and overall quality of life. Neurocognitive assessment plays a critical role in determining what remedial or specialized instruction is needed in childhood ALL survivors and should be included as a standard part of long-term follow-up care.