Spinal Cord Stimulation to Improve Motor Function in People with Post-Stroke Hemiplegia

脊髓刺激可改善中风后偏瘫患者的运动功能

• 批准号: 10512143
• 负责人: Marco Capogrosso
• 金额: $ 165.82万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-08 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10512143
• 关键词: Activities of Daily Living; Affect; American; Animal Model; Articular Range of Motion; Axon; Behavior Therapy; Behavioral; Brain; Cervical; Cervical spinal cord structure; Cervical spine; Chronic; Clinical; Clinical Trials; Clinical assessments; Collaborations; Data; Devices; Electroencephalography; Feasibility Studies; Fiber; Forearm; Goals; H-Reflex; Hand; Hemiplegia; Home; Human; Implant; Implantation procedure; Individual; Industrialization; Institutional Review Boards; Intervention; Joints; Label; Lateral; Leg; Lesion; Link; Locomotion; Measures; Motivation; Motor; Motor Neurons; Movement; Neurostimulation procedures of spinal cord tissue; Operative Surgical Procedures; Outcome Assessment; Pain; Paralysed; Paresis; Patients; Performance; Persons; Phase; Physical therapy; Physiologic pulse; Randomized; Recovery; Residual state; Sensory; Spinal; Spinal Cord; Spinal cord injury; Stroke; Support System; System; Testing; Therapeutic; Time; Torque; Training; Validation; Weight-Bearing state; Work; arm; chronic stroke; comparative efficacy; design; dexterity; efficacy study; efficacy testing; grasp; hemiparesis; human data; human subject; implantation; improved; motor control; motor deficit; motor function improvement; motor impairment; motor recovery; neuroregulation; novel; off-label use; post stroke; preclinical study; primary outcome; prospective; recruit; safety testing; secondary outcome; social; statistics; stroke hemiparesis; stroke rehabilitation; stroke survivor; synergism; targeted treatment; white matter damage

SUMMARY Motivation: In the US, almost 800’000 people have a stroke every year. Unfortunately, despite intense physio- therapy stroke survivors retain permanent arm motor deficits, some complete hemiparesis. Project Goal: Here we aim at testing the efficacy of a system delivering electrical neurostimulation to the cervi- cal spinal cord (SCS) to improve arm and hand motor control in people with chronic post-stroke hemiparesis Hypothesis: SCS of the lumbosacral circuits below the lesion immediately restored leg movements and weight bearing locomotion in humans with spinal cord injury by increasing strength and function. Moreover, SCS com- bined to physical therapy led to long-term improvements that improved motor control even when the stimulation was turned off. In stroke the spinal circuits controlling arm and hand movements are intact and located below the brain lesion. Therefore, we hypothesize that SCS targeting the cervical spinal cord will enable people with post-stroke hemiparesis to produce functional arm and hand movements, and that these improvements will en- able the administration of a tailored behavioral training leading to superior long-term motor recovery. Preliminary data: We implanted a human subject with post-stroke hemiparesis with lateral cervical spinal leads and showed that SCS substantially improved, strength at every joint of the arm and hand, range of motions, dexterity, clinical assessment scales (Fugl-Meyer +13) and functional abilities. Moreover, SCS did not induce pain or discomfort at intensities that were necessary to obtain motor improvements. Finally, our industrial partner (CorTec GmbH), is finalizing the tests to obtain IDE approval of a fully implantable pulse generator tailored to SCS of the cervical spinal cord. Approach: In the UG3 phase of our proposal (years 1 to 3) we will finalize the necessary validation on our implantable cervical stimulator to obtain IDE approval. In parallel we will perform a pilot 30 days trial with con- ventional clinical leads used off-label in subjects with stroke to optimize SCS implant procedures and SCS pa- rameters for maximization of arm functional movements. Finally, in the last 2 years during the UH3 phase we will execute an early feasibility study testing the efficacy of cervical SCS in combination with 4 weeks of physical therapy to improve arm motor control in up to 20 subjects with chronic post-stroke hemiparesis. Perspective: Our clinical trial will be the first to assess the efficacy of neurostimulation therapies targeting the spinal cord in patients with severe hemiparesis, potentially leading to a paradigm-shift in stroke rehabilitation. 1

总结 动机：在美国，每年有近80万人中风。不幸的是，尽管有强烈的生理- 治疗中风幸存者保留永久性手臂运动缺陷，一些完全轻偏瘫。 项目目标：在这里，我们的目的是测试一个系统提供电神经刺激到cervi的有效性。 calspinal cord（SCS）改善慢性卒中后轻偏瘫患者手臂和手部运动控制 假设：病变下方腰骶回路的SCS立即恢复了腿部运动和体重 通过增加力量和功能来帮助脊髓损伤的人进行运动。此外，SCS com- 结合物理治疗导致了长期的改善，即使刺激 被关掉了在中风中，控制手臂和手运动的脊髓回路是完整的，位于下方。 脑损伤因此，我们假设SCS靶向颈脊髓将使患有 中风后轻偏瘫产生功能性手臂和手部运动，这些改善将使 能够进行量身定制的行为训练，从而实现上级长期运动恢复。 初步数据：我们在一名中风后轻偏瘫患者体内植入了颈椎侧位电极导线 并显示SCS显著改善了手臂和手的每个关节的力量，运动范围， 灵活性、临床评估量表（Fugl-Meyer +13）和功能能力。此外，SCS未诱导 获得运动改善所需强度的疼痛或不适。最后，我们的工业合作伙伴 （CorTec GmbH），正在完成测试，以获得IDE批准的完全植入式脉冲发生器， 颈脊髓束。 方法：在我们提案的UG 3阶段（第1年至第3年），我们将完成对我们的提案的必要验证 植入式颈椎刺激器获得IDE批准。同时，我们将进行为期30天的试点试验， 常规临床电极导线标签外用于卒中受试者，以优化SCS植入手术和SCS治疗， 最大化手臂功能运动的参数。最后，在UH 3阶段的最后两年， 将进行一项早期可行性研究，测试颈椎SCS与4周体格检查相结合的疗效。 在多达20例慢性卒中后轻偏瘫受试者中， 观点：我们的临床试验将是第一个评估神经刺激疗法的有效性的试验。 严重轻偏瘫患者的脊髓，可能导致中风康复的范式转变。 1