Longitudinal, Objective Measurement and Analysis of Sleep-Wake Patterns in NF1 Patients
Abstract
Neurofibromatosis 1 (NF1) affects approximately 1 in 3,500 individuals. Patients with NF1 are predisposed to multiple complications, including tumors of the nervous system (neurofibromas optic gliomas, malignant astrocytomas) and neuronal dysfunction (learning disabilities, attention deficits). While the tumor aspects of NF1 have received much attention from researchers, other common but less serious symptoms affect individuals with NF1 and can influence the quality of life. Among these, sleep disturbances are commonly reported symptom in NF1 patients. Disrupted sleep may contribute to an overall poor quality of life and additionally may contribute to the other symptoms of NF1. Studies in NF1 knockout model organisms (mice and fruit flies) suggest that sleep disruption in NF1 may reflect a fundamental role for the neurofibromin protein (encoded by the NF1 gene) in the functioning of the molecular clock, which serves to coordinate our internal time (body clock) with the external rhythm (day/night cycle). To date, there have been no true scientific measurements of timing, quantity, and quality of sleep in NF1 patients, with previous studies relying on questionnaires to collect data. The problems of NF1 are extremely variable, with individuals experiencing different symptoms to varying degrees. This study will address how prevalent sleep disruption is among people with NF1 and define the specific aspects of sleep that are affected. First, we will recruit individuals with NF1 and non-affected siblings/other family members for the study. This will be done locally at Massachusetts General Hospital and also nationally (through advertising via the NF Network and Children’s Tumor Foundation). Sleep characteristics will be assessed in a large number (>100) individuals with NF1 and healthy control (>100) subjects. Sleep/wake behavior will be evaluated for subjects over 2 weeks using an Actiwatch (a specialized device for continuous monitoring of wrist movements that resembles a watch in its appearance) and using sleep diaries. More comprehensive sleep assessments will be conducted in a subgroup of NF1 patients and matched controls. Home-based polysomnography (PSG) studies will involve wearing a nonintrusive headset for one night to record brain waves, as well as eye and leg movements to provide more precise measurements of sleep. We will carry out an assay called the Dim Light Melatonin Onset (DLMO) test to indicate whether individuals with NF1 have a circadian rhythm disruption (this involves collecting saliva at different time points in light/dark). We will also biobank blood samples from patients and healthy controls to enable NF1 genotyping and examine the relative levels of gene expression that may impinge on sleep/wake behavior. Risks for patients are minimal since, other than collecting blood, all of the studies are non-invasive and observational. This study would be the first to use objective data gathering methods to study sleep in NF1 patients. Our detailed analysis may reveal particular aspects of sleep being affected. Further, the findings may suggest interventions to help increase quality of life, e.g., sleep medication or a change in life style.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010776
Entities
People
- Richa Saxena
Organizations
- Massachusetts General Hospital
- United States Army