Cognitive functioning and pain interference mediate pain predictive effects on health-related quality of life in pediatric patients with Neurofibromatosis Type 1.

OBJECTIVES: The objective was to investigate the serial mediating effects of perceived cognitive functioning and pain interference in daily living in the relationship between perceived pain and overall generic health-related quality of life (HRQOL) in children, adolescents, and young adults with Neurofibromatosis Type 1 (NF1). METHODS: The Pain, Cognitive Functioning, and Pain Impact Scales from the PedsQL Neurofibromatosis Type 1 Module and the PedsQL 4.0 Generic Core Scales were completed in a multi-site national study by 323 patients ages 5-25 and 335 parents. A serial multiple mediator model analysis was conducted to test the hypothesized sequential mediating effects of cognitive functioning and pain interference as intervening variables in the association between pain as a predictor variable and overall generic HRQOL. RESULTS: Pain predictive effects on overall generic HRQOL were serially mediated by cognitive functioning and pain interference. In predictive analytics models utilizing hierarchical multiple regression analyses with age and gender demographic covariates, pain, cognitive functioning and pain interference accounted for 66% of the variance in patient-reported generic HRQOL and 57% of the variance in parent proxy-reported generic HRQOL (P < 0.001), reflecting large effect sizes. CONCLUSIONS: Cognitive functioning and pain interference explain in part the mechanism of pain predictive effects on overall generic HRQOL in pediatric patients with NF1. Identifying NF1-specific pain, cognitive functioning, and pain interference as salient predictors of overall generic HRQOL from the patient and parent perspective facilitates a family-centered orientation to the comprehensive care of children, adolescents, and young adults with NF1.

Speech difficulties and patient health communication mediating effects on worry and health-related quality of life in children, adolescents, and young adults with Neurofibromatosis Type 1.

The objective was to investigate the serial mediating effects of speech difficulties, patient health communication, and disease-specific worry in the relationship between neurofibromatosis (NF) symptoms (pain and skin symptoms) and total generic health-related quality of life (HRQOL) in children, adolescents, and young adults with NF Type 1 (NF1) from the patient perspective. The Speech, Communication, Worry, Pain, Skin Itch Bother, and Skin Sensations Scales from the Pediatric Quality of Life Inventory (PedsQL) NF1 Module and the PedsQL 4.0 Generic Core Scales were completed in a multi-site national study by 305 patients ages 5-25 years. A serial multiple mediator model analysis was conducted to test the hypothesized sequential mediating effects of speech difficulties, health communication, and worry as intervening variables in the association between NF1 symptoms and HRQOL. Symptoms predictive effects on total generic HRQOL were serially mediated by speech difficulties, patient health communication, and worry. In predictive analytics models utilizing hierarchical multiple regression analyses with age and gender demographic covariates, the pain, skin itch bother, and skin sensations multiple mediator models accounted for 61%, 59%, and 56% of the variance in generic HRQOL (p < .001), reflecting large effect sizes. Speech difficulties, patient health communication, and disease-specific worry explain in part the mechanism of symptoms predictive effects on total generic HRQOL in pediatric patients with NF1. Identifying NF1-specific predictors and serial mediators of total generic HRQOL in pediatric patients with NF1 from the patient perspective enables a patient-centered comprehensive care approach for children, adolescents, and young adults with NF1.

Psychosocial Features of Neurofibromatosis Type 1 in Children and Adolescents.

Neurofibromatosis type 1 (NF1) is a common neurologic condition associated with a wide variety of developmental deficits that have an important impact on children and adolescents. OBJECTIVE: This article aims to document the psychosocial features of NF1 and to report the interventions described to address the needs of pediatric patients with NF1. METHODS: A literature review was conducted concerning the social life, mental health, and quality of life (QOL) of children and adolescents with NF1 as well as the psychosocial interventions addressed to this population. RESULTS: Compared to unaffected children and adolescents of the general population, pediatric patients with NF1 have an increased risk of having social difficulties, mental health disorders, behavioral and emotional problems, as well as diminished QOL. Only 3 articles describe interventions within the NF1 population to address these difficulties. CONCLUSION: There is a need to develop and assess psychosocial interventions for patients with NF1.

Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients.

BACKGROUND: Cognitive difficulties are the most common neurological complications in neurofibromatosis type 1 (NF1) patients. Recent animal models proposed increased GABA-mediated inhibition as one underlying mechanism directly affecting the induction of long-term potentiation (LTP) and learning. In most adult NF1 patients, apparent cognitive and attentional deficits, tumors affecting the nervous system and other confounding factors for neuroscientific studies are difficult to control for. Here we used a highly specific group of adult NF1 patients without cognitive or nervous system impairments. Such selected NF1 patients allowed us to address the following open questions: Is the learning process of acquiring a challenging motor skill impaired in NF1 patients? And is such an impairment in relation to differences in intracortical inhibition? METHODS: We used an established non-invasive, double-pulse transcranial magnetic stimulation (dp-TMS) paradigm to assess practice-related modulation of intracortical inhibition, possibly mediated by gamma-minobutyric acid (GABA)ergic-neurotransmission. This was done during an extended learning paradigm in a group of NF1 patients without any neuropsychological deficits, functioning normally in daily life and compared them to healthy age-matched controls. FINDINGS: NF1 patients experienced substantial decline in motor skill acquisition (F = 9.2, p = 0.008) over five-consecutives training days mediated through a selective reduction in the early acquisition (online) and the consolidation (offline) phase. Furthermore, there was a consistent decrease in task-related intracortical inhibition as a function of the magnitude of learning (T = 2.8, p = 0.014), especially evident after the early acquisition phase. INTERPRETATIONS: Collectively, the present results provide evidence that learning of a motor skill is impaired even in clinically intact NF1 patients based, at least partially, on a GABAergic-cortical dysfunctioning as suggested in previous animal work.

Children and adolescents with neurofibromatosis 1: a behavioral phenotype.

Twenty 6- to 17-year-old children with neurofibromatosis 1. (NF1) were compared to 20 age- and sex-matched siblings on a wide range of neuropsychological and behavioral dimensions. In familial cases, diagnostic status was confirmed by gene linkage with greater than 98% accuracy. Visual examinations that included assessments of visual evoked responses (VER) were performed on subjects with NF1. Forty-two percent of NF1 subjects had abnormal VER and underwent magnetic resonance imagery or computed tomography scans of the brain. On a variety of skills, subjects with NF1 performed more poorly than unaffected siblings. Children with NF1 were found to be less competent on measures of cognitive, language, and motor development, visual-spatial judgment, visual-motor integration, and academic achievement. Learning disabilities were common in children with NF1. Parents and teachers reported that NF1 subjects had internalizing problems and difficulty interacting with peers. A behavioral phenotype for NF1 and recommendations for preventative interventions are proposed.