Research 2-Carlson

研究2-卡尔森

• 批准号: 10468697
• 负责人: Andrew Phillip Carlson
• 金额: $ 26.08万
• 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/10468697
• 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; antagonist; 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.

项目摘要/摘要