Improving mechanistic understanding of responsiveness to spinal cord stimulation after spinal cord injury

提高对脊髓损伤后脊髓刺激反应机制的理解

• 批准号: 10672452
• 负责人: Andrew Craig Smith
• 金额: $ 12.72万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672452
• 关键词: Address; Axon; Bilateral; Biological Markers; Case Study; Classification; Clinical Management; Electromyography; Event; Foundations; Funding; Generations; Goals; Handedness; Health; Human; Implant; Individual; Injury; Institution; Intervention; Investigation; Ipsilateral; Knowledge; Leg; Life Expectancy; Light; Lower Extremity; Magnetic Resonance Imaging; Manuscripts; Measures; Motor; Movement; Muscle; National Institute of Child Health and Human Development; Neuronal Plasticity; Neurostimulation procedures of spinal cord tissue; Operative Surgical Procedures; Participant; Pattern; Persons; Physical Function; Pilot Projects; Productivity; Prognosis; Quality of life; Recovery; Reporting; Research; Research Personnel; Residual state; Resolution; Sensory; Side; Signal Transduction; Spinal Cord; Spinal cord damage; Spinal cord injury; Supine Position; Time; Tissues; Touch sensation; Training; Travel; United States National Institutes of Health; Walking; Work; biomarker identification; clinical examination; cohort; cost; design; electric field; implantation; improved; improved outcome; magnetic resonance imaging biomarker; man; neural network; neuroimaging; neuroimaging marker; neuroregulation; personalized approach; physically handicapped; prospective; rehabilitation research; sound; theories; tool; treatment strategy; trend

PROJECT SUMMARY / ABSTRACT Spinal cord injury (SCI) is a devastating event in terms of a person’s health, physical function, costs (direct and indirect), and life expectancy. It has been conventionally thought that individuals with severe SCIs, with no motor function below the level of injury, will not recover the ability to functionally move their lower extremities or voluntarily walk. However, spinal cord stimulation (SCS) has emerged as a promising intervention challenging this long-held assumption. While spinal cord stimulation allows for restored voluntary movement after severe SCI, there is a lack of mechanistic understanding regarding how it works and why some individuals respond better than others. Thus, the overall objective of this proposal is to apply neuroimaging biomarkers to generate fundamental knowledge regarding responsiveness to spinal cord stimulation (SCS). Aim 1: Use neuroimaging biomarkers to understand responsiveness to epidural SCS in participants with severe SCI, during volitional movement and standing tasks. Using high-resolution MRI in a prospective design, the applicant hypothesizes that the laterality of cord damage, detected prior to surgical implantation, will predict ipsilateral lower extremity muscle responsiveness to epidural SCS prior to any training. Aim 2: Use neuroimaging biomarkers to understand responsiveness to transcutaneous SCS in participants with severe SCI, during volitional movement tasks and sensory examination. Using high- resolution MRI in a prospective design, the applicant hypothesizes that total spinal cord spared tissue will predict bilateral lower extremity muscle responsiveness to transcutaneous SCS prior to any training, and that posterior cord spared tissue will predict light touch sensory recovery prior to any training. Significance: Successful completion of these Aims will advance the NIH/NICHD NCMRR aim: “to enhance the health, productivity, independence, and quality of life of people with physical disabilities.” One important problem in the field of SCS is a lack of foundational knowledge on why the intervention works. Neuroimaging holds pronounced potential to address this problem. Neuroimaging biomarkers will not only improve the understanding of responsiveness to this intervention after SCI, but will also help drive individualized approaches for using SCS, selection of epidural versus transcutaneous SCS, prognosis for improvement using SCS, and the identification of who is likely to optimally respond before activity-based recovery training. Completion of the proposed aims will lead to the high likelihood of sustained, powerful influence on the SCS field, laying a vital foundation for using MRI biomarkers to guide SCS intervention, ultimately improving the clinical management of persons with SCI.

项目概要/摘要 脊髓损伤（SCI）对于一​​个人的健康、身体功能、成本（直接和损失）来说是一种毁灭性事件。 间接）和预期寿命，传统上认为患有严重 SCI 的人没有运动能力。 功能低于受伤水平，将无法恢复移动下肢的功能或 然而，脊髓刺激（SCS）已成为一种有前途的干预措施，但具有挑战性。 这种长期存在的假设虽然脊髓刺激可以在严重的情况下恢复随意运动。 SCI，对其如何运作以及为什么有些人会做出反应缺乏机制理解 因此，该提案的总体目标是应用神经影像生物标志物来生成。 有关脊髓刺激（SCS）反应的基础知识。 目标 1：使用神经影像生物标记物了解患有以下疾病的参与者对硬膜外 SCS 的反应 严重 SCI，在前瞻性运动和站立任务中使用高分辨率 MRI。 设计中，申请人率先在手术植入之前检测到的脊髓损伤的侧向性将 在任何训练之前预测同侧下肢肌肉对硬膜外 SCS 的反应。 目标 2：使用神经影像生物标志物了解患者对经皮 SCS 的反应 患有严重脊髓损伤的参与者，在进行意志运动任务和感觉检查时使用高强度。 在前瞻性设计中分辨率 MRI，申请人希望总脊髓幸免组织能够预测 在任何训练之前，双侧下肢肌肉对经皮 SCS 的反应性，以及后侧 在任何训练之前，未受损伤的脐带组织将预测轻触感觉的恢复。 意义：成功完成这些目标将推进 NIH/NICHD NCMRR 的目标：“增强 身体残疾者的健康、生产力、独立性和生活质量是一个重要问题。” SCS 领域缺乏关于神经影像学干预为何有效的基础知识。 神经影像生物标志物具有解决这一问题的巨大潜力，这不仅会提高人们的理解。 SCI 后对这种干预措施的反应，但也将有助于推动使用 SCS 的个性化方法， 硬膜外 SCS 与经皮 SCS 的选择、使用 SCS 改善预后以及识别 谁可能在基于活动的恢复训练之前做出最佳反应。 极有可能对南海领域产生持续、强大的影响，为利用 MRI 生物标志物指导 SCS 干预，最终改善 SCI 患者的临床管理。

项目成果

The presence or absence of midsagittal tissue bridges and walking: a retrospective cohort study in spinal cord injury.

中矢状组织桥的存在或不存在和行走：脊髓损伤的回顾性队列研究。

• DOI: 10.1038/s41393-023-00890-6
• 发表时间: 2023
• 期刊: Spinal cord
• 影响因子: 2.2
• 作者: Thornton,WA;Marzloff,G;Ryder,S;Best,A;Rasheed,K;Coons,D;Smith,AC
• 通讯作者: Smith,AC

Needs of an uninsured equity-deserving minority patient cohort with physical disabilities during the first wave of the COVID-19 pandemic.

• DOI: 10.3389/fresc.2023.1000838
• 发表时间: 2023
• 期刊: FRONTIERS IN REHABILITATION SCIENCES
• 作者: Claus, D.;Draganich, C.;Berliner, J.;Niehaus, W.;Berliner, J.;Magnusson, D.;Smith, A. C.
• 通讯作者: Smith, A. C.

Muscle adaptations in acute SCI following overground exoskeleton + FES training: A pilot study.

• DOI: 10.3389/fresc.2022.963771
• 发表时间: 2022
• 期刊: FRONTIERS IN REHABILITATION SCIENCES
• 作者: Hohl, Kristen;Smith, Andrew C.;Macaluso, Rebecca;Giffhorn, Matthew;Prokup, Sara;O'Dell, Denise R.;Kleinschmidt, Lina;Elliott, Jim M.;Jayaraman, Arun
• 通讯作者: Jayaraman, Arun