Identifying and Treating Arousal-Related Deficits in Neglect and Dysphagia

描述（由申请人提供）：本R21，探索性申请将从单侧忽视研究中获得的见解应用于研究和治疗痛饮。长期目标是建立一种针对这两种疾病的药物治疗方法，可以在中风亚急性期应用，此时忽视和吞咽困难是康复的最大问题。具体目的是研究刺激强度的感知（大小估计）如何被低唤醒改变，以及大小估计的改变如何解释忽视和吞咽困难的各个方面。最后一个具体的目的是确定一种被批准用于治疗睡眠障碍的药理学药物（莫达非尼，Provigil）是否可以用于改善忽视和吞咽障碍的觉醒相关缺陷。这项研究意义重大，可以对公众健康产生直接和即时的影响。忽视和吞咽困难都是常见的，与中风相关的致残状况，每年在美国影响多达30万患者。这两种疾病都阻碍康复，并分别使患者因跌倒或吸入性肺炎而遭受额外伤害和住院的风险增加。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、忽视和吞咽困难来验证我们的目标；被证明可以暂时提高唤醒和改善忽视。我们还将使用治疗逆转的安慰剂对照研究设计来检验暂时的改善是否可以识别长期对莫达非尼（Provigil）治疗有反应的患者。这项研究可以产生突破性的发现，既可以理解吞咽困难的吞咽损害，也可以为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的管理提供帮助。该提案旨在通过建立一个可立即提供给中风患者的忽视和吞咽困难的药理学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%的中风患者要么被忽视，要么有吞咽困难，要么两者都有。忽视是不良康复结果的主要预测因素，也是由于跌倒造成额外伤害的主要原因。吞咽困难可导致呼吸系统并发症、吸入性肺炎，甚至死亡。目前还没有广泛有效的药物治疗这两种疾病。

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.