Effects of Hypoglossal Nerve Stimulation on Cognition & Language in Down Syndrome

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Project Summary/Abstract Down syndrome (DS) is one of the most common genetic conditions in the United States with a prevalence rate estimated at 6.7 people with DS per 10,000 of the population in 20101 and is characterized by global developmental delays, intellectual disability, and obstructive sleep apnea (OSA),2,3 which may be linked to severe impairments in speech and language domains for those with DS.4 Hypoglossal nerve stimulation (HGS) is a novel therapy for OSA in adults and children.5,6 Since 2015, Massachusetts Eye and Ear (MEEI) has conducted a multi-center FDA-approved Phase 1 clinical trial examining the effects of HGS on children and adolescents ages 10-21 with DS and has shown to diminish OSA. The primary outcome is implant safety while secondary measures are changes in the standard measure of OSA called the Apnea Hypopnea Index. Following qualitative parental reports of speech and language improvement, formal language testing using a procedure called Expressive Language Sampling (ELS) and neurocognitive testing (NCT) were conducted on 5 children children prior to surgery and then 3-6 months post HGS. Results showed an improvement in their IQs, in the diversity of vocabulary and complexity of syntax in spoken language, as well as in several neurocognitive domains. However, despite this promising data, more rigorous testing is needed with a larger sample size to demonstrate the significance of these findings in a rigorous fashion. This proposed study focuses on the effects on neurocognition and expressive language before and after hypoglossal nerve stimulation (HGS) treatment of Obstructive Sleep Apnea (OSA) for 57 children and adolescents who are 10 to 21 years of age. Our aims include: (1) we will test if the treatment of severe OSA with HGS significantly improves the neurocognition of patients with DS. Our hypothesis is that HGS, by improving sleep and thereby facilitating memory consolidation, will result in patients with DS having an improvement of at least 0.5 SD from baseline neurocognitive measures. The primary outcomes of the study will be five neurocognitive measures collected pre-operatively and at 6 months postoperatively: brief attention, sustained attention, processing speed, verbal intelligence, and executive functioning; and (2) we will test if the treatment of severe OSA with HGS significantly improves the expressive language skills (ELS) of patients with DS. Our hypothesis is that HGS, by strengthening the motor tone of the tongue musculature, will result in patients with DS having an improvement of at least 0.5 SD on the ELS measures. The two primary outcomes will be a measure of the diversity of vocabulary and a measure of syntactic complexity, each derived from an ELS narrative, or storytelling procedure. Narrative samples will be collected pre-operatively and then 6 months post-operatively at each site and sent to a central site where blinded investigators will transcribe and analyze the samples of expressive language.