Identifying and Treating Arousal-Related Deficits in Neglect and Dysphagia

描述(申请人提供)：此R21，探索性应用程序将应用从单侧忽视研究中获得的洞察力到吞咽障碍的调查和治疗中。长期目标是建立一种针对这两种疾病的药物治疗方法，可用于中风的亚急性阶段，此时忽视和吞咽困难是康复最难解决的问题。具体目的是调查低觉醒如何改变对刺激强度的感知(幅度估计)，以及幅度估计的改变如何解释忽视和吞咽困难的方面。最后一个具体目标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，普罗吉)是否可以用于改善与觉醒相关的忽视和吞咽障碍。这项研究意义重大，可以对公众健康产生直接和立竿见影的影响。忽视和吞咽困难都是常见的，与中风相关的致残状况，在美国每年影响多达30万名患者。这两种疾病都阻碍了康复，并分别增加了患者因跌倒或吸入性肺炎而遭受额外伤害和住院的风险。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；结果表明，这可以暂时提高觉醒和改善忽视。我们还将使用治疗逆转的安慰剂对照研究设计，检查暂时的改善是否可以确定对莫达非尼(普罗吉)治疗有长期反应的患者。这项研究可以为了解吞咽困难的吞咽障碍以及对美国成千上万在康复治疗中遭受忽视和吞咽困难的中风患者的管理带来突破性发现。公共卫生相关性：项目简介这项提案旨在通过建立一个可立即提供给中风患者的疏忽和吞咽困难的药物治疗标准来改善美国的公共健康。在美国，每年有60万中风患者受到影响。20%到45%的中风患者要么有疏忽，要么有吞咽困难，要么两者兼有。忽视是康复效果差的主要预测因素，也是跌倒造成额外伤害的主要原因。吞咽困难可导致呼吸道并发症、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.