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

项目总结/摘要 唐氏综合症（DS）是美国最常见的遗传疾病之一， 2010年的患病率估计为每10，000人中有6.7人患有DS 1，其特点是 全球发育迟缓、智力残疾和阻塞性睡眠呼吸暂停（OSA），2，3可能与 对于那些患有DS的人来说，言语和语言领域的严重障碍。 舌下神经刺激（HGS）是一种治疗成人和儿童OSA的新型疗法。5，6自2015年以来， 马萨诸塞州眼耳（MEEI）进行了一项多中心FDA批准的1期临床试验 研究HGS对10-21岁儿童和青少年DS的影响，并显示其可减少 OSA。主要结局是植入物安全性，而次要指标是标准指标的变化 称为呼吸暂停低通气指数根据父母对言语和语言的定性报告， 改进，使用称为表达性语言采样（ELS）的程序进行正式语言测试， 对5名儿童在术前和术后3-6个月进行神经认知测试（NCT HGS。结果表明，他们的智商，词汇的多样性和句法的复杂性有所提高， 口语，以及在几个神经认知领域。然而，尽管有这些令人鼓舞的数据， 需要用更大的样本量进行严格的测试，以证明这些发现在 严谨的时尚本研究的重点是神经认知和表达语言的影响 舌下神经刺激（HGS）治疗阻塞性睡眠呼吸暂停（OSA）57例 10至21岁的儿童和青少年。我们的目标包括：（1）我们将测试是否治疗 重度OSA合并HGS可明显改善DS患者的神经认知功能。我们的假设是 HGS通过改善睡眠，从而促进记忆巩固， 与基线神经认知测量相比，改善至少0.5 SD。的主要结局 本研究将在术前和术后6个月收集5项神经认知指标：简要 注意力、持续注意力、处理速度、言语智能和执行功能;（2）我们将 测试HGS治疗重度OSA是否显著改善表达语言技能 (ELS)DS患者。我们的假设是HGS通过加强舌头的运动张力 肌肉组织，将导致DS患者在ELS测量上至少改善0.5 SD。 两个主要的结果将是衡量词汇的多样性和衡量句法 复杂性，每一个都来自ELS叙事或讲故事的过程。将收集叙述样本 术前和术后6个月在每个研究中心进行，并送至设盲的中心研究中心 研究人员将转录和分析表达性语言的样本。

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.