Identifying and Treating Arousal-Related Deficits in Neglect and Dysphagia

描述（由申请人提供）：该R21探索性应用将从单侧忽视研究中获得的见解应用于吞咽困难的研究和治疗。长期目标是建立一种药物治疗这两种疾病，可以应用在亚急性期的中风时，忽视和吞咽困难是最有问题的康复。具体的目的是调查如何感知刺激强度（幅度估计）被低觉醒改变，以及如何改变幅度估计占忽视和吞咽困难的方面。最后一个具体的目的是确定是否批准用于治疗睡眠障碍的药物（莫达非尼，Provigil）可用于改善忽视和吞咽困难的觉醒相关缺陷。这项研究意义重大，可以对公众健康产生直接和直接的影响。忽视和吞咽困难都是与中风相关的常见致残性疾病，在美国每年影响多达30万患者。这两种疾病都阻碍康复，并且分别由于福尔斯或吸入性肺炎而使患者处于额外损伤和住院的风险增加。对于这两种疾病都没有广泛有效的药物治疗形式。我们计划通过测量单侧中风患者在热量刺激前后的觉醒、幅度估计、忽视和吞咽困难来测试我们的目标;显示暂时增加觉醒并改善忽视。我们还将研究，使用安慰剂对照的研究设计与治疗逆转，是否暂时改善可以识别患者谁对莫达非尼（Provigil）治疗的长期反应。这项研究可以产生突破性的发现，既可以理解吞咽障碍的吞咽障碍，也可以管理美国数千名在康复治疗期间遭受忽视和吞咽困难的中风患者。 公共卫生相关性： 该提案旨在通过建立一个可以立即提供给中风患者的忽视和吞咽困难的药物治疗标准来改善美国的公共卫生。在美国，中风每年影响60万患者。20%到45%的中风患者患有忽视、吞咽困难或两者兼而有之。新生儿是不良康复结局的主要预测因素，也是福尔斯导致额外损伤的主要原因。吞咽困难可导致呼吸系统并发症、吸入性肺炎，甚至死亡。目前对于这两种疾病都没有广泛有效的药物治疗。

DESCRIPTION (provided by applicant): This R21, exploratory application will apply insights gained from studies of unilateral neglect to the investigation and treatment of dsyphagia. The long term goal is to establish a pharmacological treatment for both disorders that can be applied during the subacute stage of stroke when neglect and dysphagia are most problematic for rehabilitation. The specific aims are to investigate how perception of stimulus intensity (magnitude estimation) is altered by hypoarousal and how an alteration of magnitude estimation accounts for aspects of neglect and dysphagia. A final specific aim is to determine whether a pharmacological agent approved to treat sleep disorders (modafinil, Provigil) can be used to improve arousal-related deficits in neglect and dsyphagia. This research is significant and it can have a direct and immediate impact on public health. Both neglect and dysphagia are common, disabling conditions associated with stroke that affect up to 300,000 patients annually in the United States. Both disorders impede rehabilitation and they place patients at increased risk for additional injury and hospitalization due either to falls or aspiration pneumonia, respectively. There is no widely effective form of pharmacological treatment for either disorder. We plan to test our aims by measuring arousal, magnitude estimation, neglect and dysphagia in unilateral stroke patients both before and after caloric stimulation; shown to temporarily increase arousal and improve neglect. We will also examine, using a placebo-controlled study design with treatment-reversal, whether temporary improvement can identify patients who respond chronically to modafinil (Provigil) therapy. This research can produce breakthrough discoveries both for understanding swallowing impairment in dysphagia and for the management of literally thousands of stroke patients in the US who suffer from neglect and dysphagia during rehabilitation therapy. PUBLIC HEALTH RELEVANCE: Project Narrative This proposal aims to improve public health in the US by establishing a pharmacological treatment standard for neglect and dysphagia that could be made available to stroke patients immediately. Stroke affects 600,000 patients annually in the United States. Between 20 and 45% of stroke patients have either neglect, dysphagia or both disorders. Neglect is a leading predictor of poor rehabilitation outcome and a major cause of additional injury due to falls. Dysphagia can lead to respiratory complications, aspiration pneumonia, and even death. There is no widely effective pharmacological treatment for either disorder at the present time.