Rational and Objectives of Proposed Research:

Persistent sleep loss or poor quality sleep can have profound effects on emotional state and behavior, cognitive function and performance at school, family cohesion, general quality of life, mental health, and physical well-being. Studies indicate that parents commonly report sleep difficulties in children with Neurofibromatosis type 1 (NF1), with the frequency of sleep disturbance estimated to be as high as 50%. We currently know very little about what is causing sleep disturbance in children with NF1, its impact on day-to-day functioning, or the sleep disorders to which children with NF1 are prone. Evidence from research involving animal models of NF1 suggest abnormalities in the biological processes involved with the sleep/wake cycle (i.e., circadian rhythms) may underlie these sleep problems. It is likely, however, that a range of biological, psychological, and environmental factors are influencing sleep in children with NF1.

The ultimate goal of our research is create a knowledge platform to enable optimal design of future intervention studies. For these studies to have the most meaningful clinical impact, we need to (1) have a better understanding of sleep and circadian rhythms and how they impact the day-to-day functioning of children with NF1 and (2) understand the underlying causes of sleep disturbance in these children. These objectives, which form our study aims, will enable future intervention studies to use appropriate and clinically relevant treatment targets, appropriate outcomes measures for measuring sleep, and will also guide the design of treatment interventions targeted at specific sleep disorders in NF1. More specifically, this study will be the first to characterize sleep disturbance in children with NF1 aged 6 to 12 years using objective measurement tools, comprehensive clinical assessment, and measurement of the sleep hormone, melatonin. We will also assess the frequency of sleep disorders in children with NF1. Our study design enables us to understand the biological and psychological processes contributing to poor sleep in these children. This is particularly important to establish so that appropriate treatments can be explored in future studies. Finally, this study will examine the negative consequences of poor sleep in NF1 with a specific focus on cognitive functions, behavior, academic skills, fatigue levels, and quality of life.

Ultimate Applicability and Contributions of Proposed Research:

This study addresses a critical need in the NF1 community and will result in advances in NF1 research and patient care. It will guide future patient management and health surveillance programs for sleep disturbance in children with NF1 by identifying (1) the types of sleep problems and sleep disorders these children are most prone to, (2) the potential risk factors, and (3) the potential negative consequences on the child’s learning, behavior, and cognitive functioning. Health professionals need to be alert to sleep problems and the potential effect they may have on the day-to-day functioning of children with NF1 so that sleep interventions and appropriate screening and referrals are put in place in the management plans of children with NF1. Results from this study will be critical for establishing guidelines for screening and management of sleep disturbance in children with NF1. Accurate identification and diagnosis of sleep difficulties in NF1 is vital to improve both short- and long-term health outcomes.

This study will also enable the identification of treatment targets for future interventions by investigating the contribution of biological, psychological, and environmental factors to sleep disturbance in children with NF1. This study will also enable us to classify children with NF1 into subgroups based on a specific sleep disorder diagnosis, thus guiding the selection of appropriate interventions for future intervention studies. Identification of the sleep disorder, rather than just the sleep problem, is essential because the choice of treatment needs to be based on the individual’s sleep disorder, not simply the presenting symptoms. Different approaches to treatment would be required for these various underlying causes. Within this context, there are a range of pharmacological and non-pharmacological interventions for various sleep disorders that have had proven success in children. Successful treatment of sleep disturbance in NF1 has the potential to improve a child’s cognitive, academic, and daily functioning.

This study will also provide important methods of objectively measuring sleep disturbance that impacts functional outcomes. Such measures may ultimately measure treatment outcome in future intervention trials that target sleep in NF1. Patient-related outcomes from this study will be significant, meaningful, and achievable within the timeframe of this award: 3 years.