脊髓损伤（SCI）是一种严重损害患者运动、感觉和自主功能的中枢神经系统疾病。我国现有SCI患者超过370万人，其中大部分患者生活无法自理，且后续治疗费用高昂，给患者家庭和社会带来沉重负担。SCI后的运动功能重建一直是临床医学中的重大挑战。传统的康复疗法在SCI后运动功能恢复方面的效果有限。随着新兴技术的发展，硬膜外电刺激（EES）疗法为SCI患者运动功能重建带来新的希望。然而，由于患者脊髓损伤部位、损伤方式的个性化特征，使其治疗效果具有很大的不确定性；此外，由于运动功能重建调控机制不清及康复过程中对二次损伤预防的认识不足，导致临床康复效果不佳。针对上述问题，本文从平台构建、临床康复等方面开展了系统性的研究工作。 首先，在神经调控国家工程研究中心团队前期脊髓电刺激器的工作基础上，设计了与EES刺激方法相关的软硬件平台，该平台支撑了EES 疗法在处理患者个性化问题过程中的调控及后续对疗法机制的研究工作。 进而，针对患者功能重建过程中调控机制不清的问题，提出了基于单脉冲诱发肌电响应的刺激参数库建立方法，提升了疗法处理患者个体化差异及状态变化的能力。在机制研究方面，定量阐释了感觉反馈及刺激参数等因素对功能重建的影响，并从脊髓反射等角度对运动功能重建机制进行了讨论。 针对患者个性化单关节运动控制失能问题，首先通过诱发复合动作电位信号解耦运动控制中各影响因素的方法证明了自主运动意图结合EES对肌肉的特异性激活作用，进而提出了自主运动意图结合靶向EES的康复方法，成功实现了患者单关节运动控制能力的恢复，该方法为临床康复提出一种新的疗法途径。 最后，针对患者康复训练中的二次损伤风险预防问题，提出了基于运动状态实时监测的闭环关节载荷调控方法，降低了患者训练过程中的二次损伤风险。进一步的，初步验证了体内刺激系统加速度信号实现患者下肢运动学监测的可行性，为后续构建仅依靠体内设备进行安全监控的系统提供了基础。 上述工作成功实现了三名SCI患者（两名创伤性ASIA B级及一名医源性ASIA C级）从运动功能完全或部分丧失到站立和行走功能恢复的突破。本文为EES疗法的实施提供了必要的软硬件平台，并为临床康复过程提供了具有靶向性、安全性等特点的EES方法，对后续的临床康复和研究工作具有重要意义。
Spinal cord injury (SCI) is a central nervous system disorder that severely impairs motor, sensory, and autonomic functions. In China, there are more than 3.7 million SCI patients, most of whom are unable to live independently, and the high costs of follow-up treatment place a heavy burden on both families and society. The restoration of motor function following SCI has long been a major challenge in clinical medicine. Traditional rehabilitation therapies have shown limited efficacy in restoring motor function after SCI. With the development of emerging technologies, epidural electrical stimulation (EES) offers new hope for motor function recovery in SCI patients. However, due to the individualized characteristics of the location and nature of spinal cord injuries, treatment outcomes remain highly uncertain. Additionally, the lack of understanding of the neuromodulation mechanisms of motor function recovery and insufficient awareness of secondary injury prevention during rehabilitation have led to suboptimal clinical outcomes. To address these issues, this study undertakes systematic research from the perspectives of platform development and clinical rehabilitation. First, building on the previous work of the National Engineering Research Center of Neuromodulation on spinal cord stimulators, a hardware and software platform related to EES stimulation methods was designed. This platform supports the application of EES therapy in addressing the individualized problems of patients and facilitates subsequent research into the mechanisms of the therapy. Furthermore, to address the unclear neuromodulation mechanisms involved in motor function recovery, a method for establishing a stimulation parameter library based on single-pulse evoked electromyographic responses was proposed. This method enhances the ability of the therapy to manage patient-specific differences and changes in their condition. In terms of mechanism research, the effects of sensory feedback and stimulation parameters on functional recovery were quantitatively explained, and the mechanisms of motor function recovery were discussed from the perspective of spinal reflexes. To address the issue of individualized joint motor control dysfunction in patients, the method of decoupling the various factors affecting motor control through evoked compound action potential (ECAP) signals was employed, demonstrating the specific role of voluntary motor intention combined with EES in muscle activation. Based on this finding, a rehabilitation method combining voluntary motor intention with targeted EES was proposed, successfully restoring the single-joint motor control abilities of patients. This method presents a novel therapeutic approach for clinical rehabilitation. Finally, in response to the challenge of preventing secondary injury during rehabilitation training, a closed-loop joint load regulation method based on real-time monitoring of motor status was proposed, effectively reducing the risk of secondary injury during training. Additionally, the feasibility of using implanted stimulation system acceleration signals for monitoring the kinematics of the lower limbs was preliminarily verified, laying the foundation for the future development of a system for safety monitoring relying solely on implanted devices. These efforts successfully achieved breakthroughs in motor function recovery in three SCI patients (two with traumatic ASIA B-level injuries and one with iatrogenic ASIA C-level injury), who progressed from complete or partial loss of motor function to standing and walking. This study provides the necessary hardware and software platform for the implementation of EES therapy and proposes a targeted and safe EES method for clinical rehabilitation, holding significant implications for future clinical rehabilitation and research.
