Project 4: Investigation of Clinical, Blood, and Neuroimaging Biomarkers as Predictors of Independent Walking Post-stroke

卒中后步行恢复的预测可以告知以患者为中心的护理和支持出院 计划。然而，当前预测模型的准确性是有限的，部分原因是研究设计较小。 以及评估的狭义预测指标。我们建议对一种新的组合进行全面评估 生物标志物可改善中风后步行恢复的预测并指导康复工作。这些 包括急性结构性脑网络破坏(利用MRI)；血液生物标记物水平(例如，脑源性 神经营养因子和血管内皮生长因子)；以及强度和临床评估 机动性。长期目标是开发一个有竞争力的资助研究计划，以优化步态 基于神经基础的步行障碍康复策略与神经术后康复 受伤。本申请的总体目标是评估研究方案的可行性并调查 选择的生物标志物和行走恢复之间的关系为更大的 卒中后独立行走的预测因素研究。拟议的目标将通过以下途径实现 具体目标如下：1)评估更大规模研究的可行性并开发远程保健数据的方法 收集；2)建立生物标志物(临床、神经影像、血液)的基线水平和平均变化 随着时间的推移；以及3)阐明生物标记物的基线水平与跨 中风后人的时间。本研究将采用纵向观察性研究设计。三十五岁 急性(3天)中风患者将从当地医疗中心招募。选择包含项 标准包括出现新的下肢无力和行走辅助；选择排除标准 包括小脑中风和MRI的禁忌症。受试者将在3个月内接受临床评估 首次出现中风症状的天数、1、4、9、12和26周。MRI扫描将在5-12天内进行 卒中后12周，卒中后72小时、1周、12周采血。评估 可行性我们将检查研究过程、招聘、资源、研究管理和科学 评估。检查急性临床、神经影像和生理指标在预测中的作用 步行康复，我们将检查这些措施与12岁时步行结果之间的关系。 中风后几周。这项研究采用了一种创新的方法来研究步行康复的预测因素。 中风后。这项拟议的研究具有重要意义，因为它有望提供强有力的科学支持 用于未来的临床试验，旨在根据预测的功能潜力进行靶向治疗。最终，这样的 知识有可能提高中风后的活动能力和患者的独立性。

Prediction of walking recovery after stroke can inform patient-centered care and support discharge planning. The accuracy of current prediction models is limited, however, due in part to small study designs and narrow predictors assessed. We propose a comprehensive evaluation of a novel combination of biomarkers to improve prediction of walking recovery and guide rehabilitation efforts after stroke. These include acute structural brain network disruption (utilizing MRI); blood biomarker levels (e.g., brain-derived neurotrophic factor and vascular endothelial growth factor); and clinical assessments of strength and mobility. The long-term goal is to develop a competitively funded research program to optimize gait rehabilitation strategies based on neural substrates of walking impairment and recovery after neurologic injury. The overall objectives in this application are to assess study protocol feasibility and investigate relationships between select biomarkers and walking recovery to provide strong justification for a larger study on predictors of independent walking after stroke. The proposed objectives will be pursued through the following specific aims: 1) Assess feasibility of a larger study and develop methods for telehealth data collection; 2) Establish baseline levels of biomarkers (clinical, neuroimaging, blood) and average change over time; and 3) Elucidate relationships between baseline levels of biomarkers and walking gains across time in persons after stroke. A longitudinal, observational study design will be utilized for this study. Thirty-five persons with acute (<3 days) stroke will be recruited from the local medical center. Select inclusion criteria include presence of new lower limb weakness and assistance for walking; select exclusion criteria include cerebellar stroke and contraindications to MRI. Subjects will undergo clinical evaluation within 3 days, 1, 4, 9, 12, and 26 weeks after the initial onset of stroke symptoms. MRI scans will occur 5-12 days and 12 weeks post-stroke, and blood draws 72 hours, 1 week, and 12 weeks post-stroke. To assess feasibility we will examine study processes, recruitment, resources, study management, and scientific assessment. To examine the role of acute clinical, neuroimaging, and physiological measures in predicting walking recovery, we will examine relationships between these measures and walking outcome at 12- weeks post-stroke. This study employs an innovative approach to investigate predictors of walking recovery after stroke. The proposed research is significant because it is expected to provide strong scientific support for future clinical trials designed to target therapies based on predicted functional potential. Ultimately, such knowledge has the potential of enhancing mobility gains and patient independence following stroke.