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

项目摘要/摘要 唐氏综合征(DS)是美国最常见的遗传性疾病之一，具有 据估计，20101每10,000人中有6.7人患有DS，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可能存在关联 对于患有DS.4的人来说，他们在言语和语言领域存在严重的障碍 舌下神经刺激(HGS)是治疗成人和儿童OSA的一种新方法。5，6自2015年以来， 马萨诸塞州眼耳公司(MEEI)进行了一项由FDA批准的多中心1期临床试验 检查HGS对10-21岁患有DS的儿童和青少年的影响，并显示出减少 奥萨。主要结果是种植体的安全性，而次要措施是标准措施的变化 被称为睡眠呼吸暂停低通气指数。遵循父母对言语和语言的质量报告 改进，使用称为表达语言采样(ELS)的过程进行正式语言测试 对5例儿童进行神经认知功能测试，分别于术前、术后3~6个月进行 HGS。结果显示，他们的智商、词汇的多样性和句法的复杂性都有所提高 口语，以及几个神经认知领域。然而，尽管数据前景看好，但更多 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。这项拟议的研究侧重于对神经认知和表达语言的影响 舌下神经刺激治疗阻塞性睡眠呼吸暂停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 重度阻塞性睡眠呼吸暂停伴HGS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，将导致DS患者 与基线神经认知测量相比，至少有0.5SD的改善。其主要成果是 这项研究将在手术前和手术后6个月收集五项神经认知测试：简要 注意力、持续注意力、处理速度、言语智力和执行功能；以及(2)我们将 HGS治疗重度阻塞性睡眠呼吸暂停是否能显著提高语言表达能力 DS患者的(ELS)。我们的假设是，通过加强舌头的运动音调，HGS 肌肉系统，将导致DS患者在ELS测量上至少有0.5SD的改善。 两个主要结果将是词汇多样性的衡量标准和句法的衡量标准 复杂性，每一种都源于ELS叙事或讲故事的过程。将收集叙事样本 分别于术前和术后6个月将患者送至中心盲点 调查人员将转录和分析这些富有表现力的语言样本。

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.