Calibrating Transcutaneous Spinal Stimulation for Spasticity, Pain, and Motor Function in SCI

项目总监/首席研究员（最后，第一，中间）：FIELD-FOTE，Edelle Carmen 项目概要/摘要 虽然脊髓损伤（SCI）的发生率可能不像其他神经系统疾病那么高，例如 中风后，许多 SCI 患者都是年轻人，他们预计将残疾生活 35 至 50 年。为此， 即使损伤的微小减少和功能的改善也会对健康产生重大影响， SCI 后的生活质量和社会参与。对于 SCI 患者来说，痉挛可能是一个严重的问题， 例如，与痉挛相关的肌肉痉挛可能非常强烈，以至于尽管有足够的运动能力 为了使用轻便的手动轮椅，有些人必须固定在笨重的电源上 椅子，以避免因痉挛而从椅子上摔下来。痉挛的治疗具有挑战性；是的 通常使用具有中枢神经系统抑制剂作用的解痉药进行治疗，但具有负面副作用 例如嗜睡、嗜睡和肌肉无力。除了痉挛之外，许多 SCI 患者还患有 神经性疼痛。除了其标志性的肌肉麻痹之外，还存在痉挛和疼痛的问题 SCI. TSS 提供了一种可同时激活多个脊髓水平的可行方法， 调节导致痉挛、疼痛和运动功能的脊髓神经回路。拟议的研究 校准经皮脊髓刺激 (TSS) 以治疗 SCI 中的痉挛、疼痛和运动功能 对这些问题产生有意义的影响的潜力。 TSS 有可能提供有价值的、并且 临床上可用的神经调节形式，具有以下优点：1）非药理学 治疗痉挛的方法，2) 用于治疗疼痛的非药物干预，以及 3) 改善 SCI 患者意志运动功能的策略。然而，在 TSS 可以被认为是 临床上可行的神经调节的可行形式，需要了解很多关于剂量反应的知识 关于刺激强度、频率和模式的关系，以及它们如何影响痉挛， 伤害性反应和意志运动输出。这些研究将成为更大规模研究的基础 完成以下目标后，将 TSS 与常用处方药物进行比较： 具体目标 1（第 1 阶段；第 1 年）量化会话中早期和晚期对所应用的 50Hz TSS 痉挛的影响 以 3 种不同强度（0.8xRT、0.8xRT-burst、1.2xRT）中的每一种强度通知第 2 阶段。 具体目标 2（第 2 阶段；第 2-5 年）量化早期、晚期、累积和持续的多期影响 3 种不同 TSS 频率条件（30Hz、50Hz、80Hz；强度/模式）的痉挛 具体目标 3（第 2 阶段；第 2-5 年）量化 3 种不同 TSS 对伤害感受的早期、晚期和持续影响 频率条件（30Hz、50Hz、80Hz） 具体目标 4（第 2 阶段；第 2-5 年）量化每次刺激对下肢的早期和持续影响 3 种不同 TSS 频率条件（30Hz、50Hz、80Hz）的肌肉力量和运动控制 OMB 编号 0925-0001/0002（修订版 01/18 批准至 03/31/2020） 第 1 页 延续格式页

Program Director/Principal Investigator (Last, First, Middle): FIELD-FOTE, Edelle Carmen PROJECT SUMMARY / ABSTRACT While the incidence of spinal cord injury (SCI) may not be as high as other neurological disorders such as stroke, many with SCI are young adults who can expect to live with disability for 35 – 50 years. For this reason, even small reductions of impairment and improvements in function can have a significant impact on health, quality of life, and social participation after SCI. Spasticity can be a significant problem for persons with SCI, for example, the muscle spasms associated with spasticity can be so strong that, despite having sufficient motor function to use a lightweight manual wheelchair, some individuals must be secured in a cumbersome power chair to avoid being thrown from the chair by their spasms. Management of spasticity is challenging; it is typically treated with antispasmodics that act as central nervous system depressants, with negative side-effects such as drowsiness, lethargy, and muscle weakness. In addition to spasticity, many individuals with SCI have neuropathic pain. The problems of spasticity and pain are in addition to the muscle paresis that is the hallmark of SCI. TSS offers an accessible approach to achieving activation of multiple spinal levels simultaneously, modulating the spinal neural circuits that underlie spasticity, pain, and motor function. The proposed studies Calibrating Transcutaneous Spinal Stimulation (TSS) for Spasticity, Pain, and Motor Function in SCI have the potential to make a meaningful impact on these problems. It is possible that TSS can offer a valuable, and clinically accessible form of neuromodulation with the benefits of providing a: 1) non-pharmacological approach for managing spasticity, 2) non-pharmacological intervention for management of pain, and 3) strategy to improve volitional motor function in persons with SCI. However before TSS can be considered a viable form of clinically accessible neuromodulation, much needs to be learned about dose-response relationships regarding intensity, frequency, and pattern of stimulation, and how these influence spasticity, nociceptive responses, and volitional motor output. These studies will be the foundation for larger studies comparing TSS to commonly prescribed pharmaceuticals, after completion of the following Aims: Specific Aim 1 (Phase 1; Year 1) Quantify early and late within-session effects on spasticity of 50Hz TSS applied at each of 3 different intensities (0.8xRT, 0.8xRT-burst, 1.2xRT) to inform Phase 2. Specific Aim 2 (Phase 2; Years 2–5) Quantify early, late, cumulative and persistent multi-session effects on spasticity of 3 different TSS frequency conditions (30Hz, 50Hz, 80Hz; at the intensity/pattern) Specific Aim 3 (Phase 2; Years 2–5) Quantify early, late, and persistent effects on nociception of 3 different TSS frequency conditions (30Hz, 50Hz, 80Hz) Specific Aim 4 (Phase 2; Years 2–5) Quantify per-stimulation, early, and persistent effects on lower extremity muscle strength and motor control of 3 different TSS frequency conditions (30Hz, 50Hz, 80Hz) OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page 1 Continuation Format Page