Research 2-Carlson

研究2-卡尔森

• 批准号: 10217160
• 负责人: Andrew Phillip Carlson
• 金额: $ 26.57万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10217160
• 关键词: Blood; Brain; Brain Injuries; Chronic; Clinical; Cognitive; Collection; Confusion; Data; Development; Dose; Drainage procedure; Electrodes; Ensure; Environment; Event; Functional disorder; Future; Goals; Human; Impaired cognition; Impairment; Ketamine; Knowledge; Language Disorders; Link; Liquid substance; Mediating; Memantine; Metabolic; Mission; Monitor; N-Methylaspartate; Nervous System Physiology; Nervous System Trauma; Neurologic; Neurologic Deficit; Neurologic Dysfunctions; Neurosurgeon; New Mexico; Operative Surgical Procedures; Outcome; Outcome Assessment; Outcome Measure; Patient Care; Patients; Pharmacotherapy; Phenotype; Physiology; Placebos; Play; Pneumonia; Postoperative Period; Prospective Studies; Randomized; Randomized Controlled Trials; Recovery; Research; Research Personnel; Risk; Role; Seizures; Stroke; Subdural Hematoma; Testing; Therapeutic; Time; Traumatic Brain Injury; United States National Institutes of Health; Universities; Work; aging population; base; behavioral outcome; clinical outcome measures; cognitive performance; cost; disability; effective therapy; efficacy testing; efficacy trial; experience; improved; improved outcome; neurological recovery; neuropsychiatry; novel; novel therapeutic intervention; older patient; pilot trial; programs; prospective; randomized trial; repaired; socioeconomics; success; synergism; targeted treatment; therapeutic target

PROJECT SUMMARY/ ABSTRACT Chronic Subdural Hematoma (cSDH) is an extremely common problem, particularly in the aging population, where fluid like collections compress the brain, frequently requiring surgical drainage. After drainage, 25-50% of patients experience post operative neurologic deficits such as weakness or confusion that are often not explained by problems such as seizure, stroke, or mass effect from the fluid and blood. Recent subdural recordings have demonstrated that some of these neurological deficits may be related to waves of spreading depolarization (SD), which cause temporary neurological dysfunction. There is a fundamental gap in knowledge as to how commonly such events are related to neurologic deficits and if they could be targeted with pharmacotherapy to improve outcomes. This knowledge gap represents an important problem because cSDH is expected to be the most common condition treated by neurosurgeons by 2030 and postoperative neurological deficits in elderly patients can have a significant impact on outcomes and secondary risks such as pneumonia and delayed mobilization. Our long-term goal is to develop effective treatments to improve recovery in these patients by targeting SD. The overall objective of this application is to examine the relationship between neurological deficits and SD and to assess feasibility of a pilot trial to determine if a strategy of NMDA-R antagonism can effectively reduce SD and improve clinical recovery. We also plan to study detailed neuropsychiatric outcomes and if these are worse in patients with SD. The central hypothesis is that SD plays a causal role in some neurologic deficits after cSDH drainage. This hypothesis is based on our preliminary data where SD was observed in 15% of such patients. In one case, repeated waves of SD were exactly time locked to development of new language deficit. Guided by this promising preliminary data, we plan to rigorously examine the relationship between SD and neurologic deficits after cSDH drainage in additional subjects (Aim #1). We will then determine feasibility of performing a randomized trial to test if a strategy of NMDA-R antagonism with a brief course of memantine effectively reduces SD and improves neurologic function (Aim #2). Finally, we will determine the time course of neuropsychiatric recovery after cSDH evacuation at day 30, 90, and 180 and assess if this is worse in patients with SD (Aim#3). We expect that these studies will provide exciting new therapeutic approaches for a previously unrecognized pathophysiology in a very common problem. These data will provide the necessary groundwork for larger pivotal trials to test efficacy of such a targeted, physiology based approach.

项目总结/摘要 慢性硬膜下血肿（cSDH）是一个非常常见的问题，特别是在老龄化人口中， 其中液体样的聚集物压迫大脑，经常需要手术引流。引流后，25-50% 的患者经历了术后神经功能缺损，如虚弱或意识模糊， 可以用癫痫、中风或液体和血液的质量效应等问题来解释。近期硬膜下 记录表明，这些神经缺陷中的一些可能与传播波有关。 去极化（SD），其引起暂时性神经功能障碍。有一个根本的差距， 了解此类事件与神经功能缺损相关的常见程度以及是否可以作为靶点 用药物治疗来改善治疗效果这种知识差距是一个重要的问题，因为 预计到2030年，cSDH将成为神经外科医生治疗的最常见疾病， 老年患者的神经功能缺损可能对结局和继发风险产生重大影响， 肺炎和延迟动员。我们的长期目标是开发有效的治疗方法来改善康复 在这些患者中进行治疗。本应用程序的总体目标是检查 之间的神经功能缺损和SD，并评估可行性的试点试验，以确定是否有一个战略， NMDA-R拮抗剂可有效降低SD，促进临床恢复。我们还计划详细研究 神经精神结局以及这些结局在SD患者中是否更糟。核心假设是SD扮演着 cSDH引流后某些神经功能缺损的因果关系。这个假设是基于我们的初步数据 其中在15%的此类患者中观察到SD。在一种情况下，SD的重复波完全时间锁定 发展新的语言缺陷。在这些有希望的初步数据的指导下，我们计划严格地 在其他受试者中检查cSDH引流后SD与神经功能缺损之间的关系（目的 #1）。然后，我们将确定进行随机试验的可行性，以测试是否NMDA-R的策略 美金刚的短期拮抗作用有效地减少了SD，改善了神经功能（目的 #2）。最后，我们将确定第30天cSDH排空后神经精神恢复的时间进程， 90和180，并评估这在SD患者中是否更差（目标3）。我们希望这些研究能够提供 令人兴奋的新的治疗方法，以前未被认识的病理生理学在一个非常常见的 问题.这些数据将为更大规模的关键性试验提供必要的基础，以测试这种药物的有效性。 有针对性的生理学方法