Examining the frontal subcortical brain vulnerability hypothesis in children with neurofibromatosis type 1: Are T2-weighted hyperintensities related to executive dysfunction?

OBJECTIVE: It was hypothesized that neuropsychological impairments in children with neurofibromatosis type I (NF1) are associated with brain areas of increased T2-weighted signal intensity on MRI. Systematic and extensive examination of this hypothesis remains however scarce, particularly regarding executive dysfunction whereas hyperintensities are located preferentially in frontal-sub-cortical networks. In this study, we compared the executive functioning profile with characteristics of brain hyperintensities in children with NF1. METHOD: A sample of 36 school-age children with NF1 (7-12 years) underwent a detailed examination of executive function, including performance-based tests and child's behavior rating in daily life. Executive function measures were compared with the characteristics of the T2-weighted hyperintensities on parallel MRI scans. The presence, number, and size of hyperintensities in the whole brain were considered as well as their main cerebral locations. RESULTS: Executive dysfunction including traditional cognitive and ecological measures in children with NF1 is not significantly influenced by T2-weighted hyperintensities, in terms of presence or not, number, size, and location, whether in the whole brain or according to involved specific brain areas. CONCLUSION: T2-weighted hyperintensities, as they are currently measured, cannot be used as a strong indicator of executive dysfunction in children with NF1. Based on the available NF1 cognitive impairment pathogenesis models, a critical discussion on anatomical-functional relationships between hyperintensities and neuropsychological profile is proposed, especially the executive dysfunction.

Is executive function specifically impaired in children with neurofibromatosis type 1? A neuropsychological investigation of cognitive flexibility.

Our study investigated spontaneous versus reactive cognitive flexibility in children with neurofibromatosis type 1 (NF1) and their comorbidity with attention-deficit hyperactivity disorder (ADHD). Thirty children with NF1 aged 7 to 12 years old were compared to 60 healthy controls matched by age, gender, and parental education. On the basis of Eslinger and Grattan's definition ( 1993 ), spontaneous shifting was assessed using fluency tests, whereas reactive flexibility was measured by a child adaptation of the Modified Card-Sorting Test and the Brixton Test. IQ and basic skills were taken into account as confounding variables that might influence executive measures. NF1 children performed below the level of healthy children on both reactive flexibility tasks, even when intelligence and basic skills were partialled out, but ADHD symptomatology was not found to adversely affect the performance of patients. Our findings support the hypothesis of a specific executive impairment in NF1, uncovering a dissociation between (impaired) reactive flexibility and (preserved) spontaneous shifting, with no impact of ADHD on executive performance.

Executive dysfunction in children with neurofibromatosis type 1: a study of action planning.

In this study, we tested the hypothesis that action planning is impaired in children with neurofibromatosis type 1 (NF1). Thirty-six children with NF1 were pair-matched to 36 healthy controls (HC) on age (range, 7-12 years), sex, and parental education level, and both groups were administered three action-planning tasks. To examine the relation of task performance to attention deficit hyperactivity disorder (ADHD), the NF1 group was divided into subsets of children who met or did not meet criteria for ADHD. Children with NF1 performed less well than HC on all planning tasks, and differences remained when controlling for IQ or a measure of visuospatial skill. Both the NF1 with ADHD subset and NF1 without ADHD subset performed more poorly than HC on two of the tasks, whereas only the NF1 with ADHD subset performed worse than HC on the third planning task. The results underscore the importance of evaluating executive function in children with NF1 and suggest that deficits in this domain may be only partially related to ADHD. Planning deficits in children with NF1 may be part of their cognitive phenotype. Identifying these deficits is relevant in determining factors contributing to learning problems and in developing appropriate interventions.