Perceived transition readiness among adolescents and young adults with neurofibromatosis type 1 and plexiform neurofibromas: a cross-sectional descriptive study.

OBJECTIVES: Neurofibromatosis type 1 (NF1) is a genetic cancer predisposition syndrome that can impact multiple organ systems and is associated with plexiform neurofibroma tumors, requiring care from birth through adulthood. Adolescents and young adults (AYAs) with NF1 face several barriers to transition from pediatric to adult care. This cross-sectional study aimed to assess transition readiness in this population and to evaluate relationships between specific NF1 symptoms and transition readiness. METHODS: AYAs (aged 16-24) enrolled in existing studies related to NF1 were eligible. AYAs and their parents completed measures of transition readiness (Transition Readiness Assessment Questionnaire version 4 [TRAQ-4]), and AYAs also completed a transition readiness interview (UNC TRxANSITION). RESULTS: Thirty-eight AYAs (mean age = 19.95 ± 2.68 years) participated in the study. Average TRAQ scores indicated that AYAs were still learning Self-Management skills (M = 3.37, SD = 1.08) and Self-Advocacy skills (M = 3.98, SD = 0.67). Older AYAs had higher TRAQ scores for Self-Management (r = 0.70, p < .001) and Self-Advocacy (r = 0.41, p = .011) than younger AYAs. Parents and AYAs had similar TRAQ scores. About one third of AYAs (37.8%, n = 14) expressed uncertainty about how NF1 might affect them in the future. The remaining AYAs mostly expressed concerns regarding tumor growth, pain, or cancer. CONCLUSIONS: In this small study, preliminary findings suggest that AYAs with NF1 express confidence in many areas of transition readiness but continue to require support, particularly with Self-Management skills. Given the gaps in understanding of future health risks, AYAs with NF1 would benefit from early assessment, psychoeducation, and support for transition readiness to adult care.

Predictors of cognitive development in children with neurofibromatosis type 1 and plexiform neurofibromas.

AIM: To describe the cognitive development of children with neurofibromatosis type 1 (NF1) and plexiform neurofibromas, and identify predictors of cognitive development. METHOD: Participants included 88 children with NF1 and plexiform neurofibromas (50 males, 38 females, aged 6-18y, mean=12y, SD=3y 7mo) on a natural history study at the National Cancer Institute. Neuropsychological assessments (e.g. IQ, academic achievement, attention, and executive functioning) were administered three times over 6 years. RESULTS: Relative to normative peers, the total sample of children with NF1 and plexiform neurofibromas demonstrated significantly lower scores in most cognitive domains and decreasing z-scores over time in math, writing, inhibitory control, and working memory. Children who had parents with (vs without) NF1 were more likely to experience decreased z-scores in performance IQ, reading, writing, attention, and working memory. Higher (vs lower) parental education was related to higher levels of IQ, math, reading, and cognitive flexibility and a slower decrease in math z-scores. Children's sex and the number of NF1 disease-related complications were not related to most cognitive outcomes. INTERPRETATION: Children with NF1 and plexiform neurofibromas are at high risk for cognitive difficulties and declining z-scores in various domains of cognitive functioning over time. The findings highlight the need for a better understanding of the within-group differences in these children and their need for individualized educational plans. WHAT THIS PAPER ADDS: Math, writing, inhibitory control, and working memory scores decreased over time. The proportion of children with clinically significant cognitive deficits increased over time. Parental neurofibromatosis type 1 and low education were related to greater cognitive difficulties in children.

Patient Reported Outcomes Measurement Information System and Quality of Life in Neurological Disorders Measurement System to Evaluate Quality of Life for Children and Adolescents with Neurofibromatosis Type 1 Associated Plexiform Neurofibroma.

OBJECTIVE: To assess the health-related quality of life of children with neurofibromatosis type 1-related plexiform neurofibromas (pNF) using a battery of patient-reported outcome measures selected based on a conceptual framework derived from input by patients, parents, and clinicians regarding the most important pNF symptoms and concerns. STUDY DESIGN: There were 140 children with pNF ages 8-17 years who completed the Patient-Reported Outcomes Measurement Information System (including domains anxiety, depressive symptom, psychosocial stress experiences, fatigue, pain interference, meaning and purpose, positive affect, peer relationships, physical function-mobility) and Quality of Life in Neurological Disorders measurement system (stigma) via an online platform. T-scores for each measure were compared with US population norms. RESULTS: Children with pNF reported significantly worse scores than the population norms on 8 of 10 domains. Children with at least 1 family member having a diagnosis of neurofibromatosis type 1 and those having pain reported significantly worse symptoms and functioning on all domains. Boys reported significantly worse pain interference, stigma, meaning and purpose, mobility function, and upper extremity function than girls. CONCLUSIONS: Children with pNF experience significantly worse health-related quality of life on all but 1 domain, highlighting the importance of monitoring children's quality of life over time in clinical research and practice. Future research should evaluate the replicability of these findings and evaluate the validity of the Patient-Reported Outcomes Measurement Information System and Quality of Life in Neurological Disorders measurement system in relation to clinical characteristics among children with pNF.

Pain interference in youth with neurofibromatosis type 1 and plexiform neurofibromas and relation to disease severity, social-emotional functioning, and quality of life.

The physical manifestations of neurofibromatosis type 1 (NF1) can cause chronic pain. This study investigated the impact of pain in youth with NF1 and plexiform neurofibromas (PNs) and its relationship to disease factors, social-emotional functioning, and quality of life (QOL) within a biopsychosocial framework. Caregivers of 59 children and adolescents with NF1 and PNs (6-18 years), and 41 of these youth (10-18 years), completed questionnaires assessing social-emotional functioning and QOL, including an item on pain interference. Measures of disease severity included total PN volume by percent body weight and number of disease complications. Both caregiver (73%) and self-report (59%) ratings indicated that pain interferes with the child's daily functioning despite 33% taking pain medication. Based on caregivers' behavior ratings, more symptoms of anxiety and larger tumor volumes predicted greater pain interference, while greater pain interference, worse depressive symptoms, and more disease complications predicted poorer QOL. As rated by adolescents, more symptoms of anxiety predicted greater pain interference, while greater pain interference and social stress predicted poorer QOL. Further, social-emotional problems mediate the relationship between pain interference and QOL. Thus, pain interferes with daily functioning in the majority of youth with NF1 and PNs even when using pain medication. The impact of pain interference, disease severity, and particularly social-emotional problems on QOL highlights the interaction between physical and psychological states in NF1. Future research and treatment of pain in this population should utilize a biopsychosocial approach and involve multidisciplinary therapies including psychological interventions that target social-emotional functioning.

Sirolimus for non-progressive NF1-associated plexiform neurofibromas: an NF clinical trials consortium phase II study.

BACKGROUND: Patients with Neurofibromatosis Type 1 (NF1) have an increased risk of developing tumors of the central and peripheral nervous system, including plexiform neurofibromas (PN), which are benign nerve sheath tumors that are among the most debilitating complications of NF1. There are no standard treatment options for PN other than surgery, which is often difficult due to the extensive growth and invasion of surrounding tissues. Mammalian Target of Rapamycin (mTOR) acts as a master switch of cellular catabolism and anabolism and controls protein translation, angiogenesis, cell motility, and proliferation. The NF1 tumor suppressor, neurofibromin, regulates the mTOR pathway activity. Sirolimus is a macrolide antibiotic that inhibits mTOR activity. PROCEDURE: We conducted a 2-stratum phase II clinical trial. In stratum 2, we sought to determine whether the mTOR inhibitor sirolimus in subjects with NF1 results in objective radiographic responses in inoperable PNs in the absence of documented radiographic progression at trial entry. RESULTS: No subjects had better than stable disease by the end of six courses. However, the children's self-report responses on health-related quality of life questionnaires indicated a significant improvement in the mean scores of the Emotional and School domains from baseline to 6 months of sirolimus. CONCLUSIONS: This study efficiently documented that sirolimus does not cause shrinkage of non-progressive PNs, and thus should not be considered as a treatment option for these tumors. This study also supports the inclusion of patient-reported outcome measures in clinical trials to assess areas of benefit that are not addressed by the medical outcomes.

Social-emotional functioning of children and adolescents with neurofibromatosis type 1 and plexiform neurofibromas: relationships with cognitive, disease, and environmental variables.

OBJECTIVE: This descriptive cross-sectional study aimed to determine how cognitive, disease, and environmental variables relate to social-emotional functioning in youth with NF1 and plexiform neurofibromas. METHODS: Psychological assessments were administered to 53 children (mean age 12.4 years); parents and teachers completed the behavior assessment system for children-second edition (BASC-2). Disease severity was quantified by nurse-practitioner ratings and tumor burden, and parents completed a life events checklist to indicate environmental stressors. RESULTS: Notable proportions of children scored in the at-risk/clinically significant ranges on several parent and teacher BASC-2 subscales including somatization, attention problems, depression, and withdrawal. Combinations of cognitive, disease, and environmental variables predicted scores on parent BASC-2 internalizing problems, behavior symptoms index, and Adaptive Skills composites. CONCLUSIONS: Cognitive, disease, and environmental variables relate to social-emotional outcomes in children with NF1. These youth may benefit from interventions targeting social skills, cognitive functioning, and adaptive ways of coping with NF1-related pain.

Verbal learning and memory in youth with neurofibromatosis type 1 and plexiform neurofibromas: Relationships with disease severity.

AIM: To provide a comprehensive characterization of verbal learning and memory (VLM) abilities in youth with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs) and to evaluate disease severity as a predictor of VLM functioning over time. METHOD: As part of a longitudinal natural history study, youth with NF1 and PNs were administered repeat neuropsychological assessments, including measures of VLM and ratings of NF1 disease severity completed by a medical professional. This sub-study analyzed data from 89 patients (M age baseline = 13.1, SD = 4.3 years, range 6-24 years) who had completed tests of VLM abilities and verbal attention at either baseline and/or 36 months. RESULTS: VLM scores across the sample fell predominantly within the average range of functioning at both time points. However, relative to peers with mild NF1 disease severity, youth with moderate/severe NF1 disease showed lower functioning across multiple VLM domains at 36 months, even after controlling for the effects of verbal attention. INTERPRETATION: Exclusive use of overall domain scores does not fully characterize VLM functioning in youth with NF1 and PNs. Additionally, children and adolescents with more severe NF1 disease should be monitored more closely for verbal memory challenges and targeted for interventions.

Repair of the lower and middle parts of the face by composite tissue allotransplantation in a patient with massive plexiform neurofibroma: a 1-year follow-up study.

BACKGROUND: The risk to benefit ratio of face transplantation with a composite tissue allograft remains debatable, although this procedure is technically feasible. We report here a 1-year follow-up of a patient who underwent face transplantation with a composite tissue allograft. METHODS: On Jan 21, 2007, a 29-year-old man with neurofibromatosis type 1 underwent resection of a massive plexiform neurofibroma diffusely infiltrating the middle and lower part of his face. The main goal was to restore both the cutaneous appearance and function of the face, including, in particular, control of orbicularis oculi and oris muscle contraction. The issues of immunosuppressive therapy, psychological outcome, and social reintergration were addressed, together with the monitoring of graft rejection by biopsies of the skin and mucosa. FINDINGS: The initial postoperative course was uncomplicated. Two episodes of clinical rejection occurred on days 28 and 64. The second episode was associated with cytomegalovirus infection. Both episodes resolved favourably, with no further clinical signs of rejection, making the reduction of immunosuppressive treatment possible. A year after surgery, the functional outcome was very good, with successful sensory and motor reinnervation in the transplanted territory. Psychological recovery was excellent, with complete social reintegration. INTERPRETATION: This case demonstrates the feasibility of surgically removing a large part of the face and replacing it with a composite tissue allograft. This facial repair procedure, which seems to have a satisfactory risk to benefit ratio, could be offered in rare and selected cases.

Impact of neurofibromatosis 1 upon quality of life in childhood: a cross-sectional study of 79 cases.

BACKGROUND: Neurofibromatosis 1 (NF1) has a significant impact on quality of life (QoL). OBJECTIVES: To evaluate QoL in NF1 according to phenotype from the viewpoint of children and proxy. METHODS: One hundred and forty families with a child aged between 8 and 16 years, seen consecutively at the National Academic Paediatric Referral Centre for NF1 for a phenotype evaluation, were contacted by mail. Families agreeing to participate were sent two questionnaires, the DISABKIDS for children and proxy and the cartoon version of the Children's Dermatology Life Quality Index (CDLQI). QoL scores were compared with those in other major diseases and were analysed according to age, gender and phenotype. RESULTS: Eighty families agreed to participate, and 79 returned the questionnaires. Using DISABKIDS, NF1 had a higher impact on health-related QoL than asthma (mean+/-SD 75.18+/-18.22 vs. 79.78+/-13.41; P=0.005). The total score was more altered when assessed by proxy than by children (71.20+/-17.94 vs. 75.18+/-18.22; P=0.002). Orthopaedic manifestations, learning disabilities and presence of at least two plexiform neurofibromas were independently associated with a higher impact (P<0.01). The CDLQI score was slightly altered (11.3%). Dermatological signs, such as café-au-lait spots and freckling, did not have a significant impact. CONCLUSIONS: Orthopaedic manifestations, learning disabilities and plexiform neurofibromas are the main complications impacting on QoL during childhood NF1. QoL could be considered as an endpoint for intervention studies in this context.