Defitech Chair of Clinical Neuroengineering, Neuro-X Institute (INX) and Brain Mind Institute (BMI), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1202 Geneva, Switzerland; Defitech Chair of Clinical Neuroengineering, Neuro-X Institute (INX) and Brain Mind Institute (BMI), Ecole Polytechnique Fédérale de Lausanne Valais (EPFL Valais), Clinique Romande de Réadaptation, 1951 Sion, Switzerland.
Clinical Neuroscience, University of Geneva Medical School, 1202 Geneva, Switzerland; Bertarelli Foundation Chair in Translational Neuroengineering, Neuro-X Institute (INX) and Institute of Bioengineering, School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Med. 2023 Sep 8;4(9):591-599.e3. doi: 10.1016/j.medj.2023.06.006. Epub 2023 Jul 11.
Around 25% of patients who have had a stroke suffer from severe upper-limb impairment and lack effective rehabilitation strategies. The AVANCER proof-of-concept clinical trial (NCT04448483) tackles this issue through an intensive and personalized-dosage cumulative intervention that combines multiple non-invasive neurotechnologies.
The therapy consists of two sequential interventions, lasting until the patient shows no further motor improvement, for a minimum of 11 sessions each. The first phase involves a brain-computer interface governing an exoskeleton and multi-channel functional electrical stimulation enabling full upper-limb movements. The second phase adds anodal transcranial direct current stimulation of the motor cortex of the lesioned hemisphere. Clinical, electrophysiological, and neuroimaging examinations are performed before, between, and after the two interventions (T0, T1, and T2). This case report presents the results from the first patient of the study.
The primary outcome (i.e., 4-point improvement in the Fugl-Meyer assessment of the upper extremity) was met in the first patient, with an increase from 6 to 11 points between T0 and T2. This improvement was paralleled by changes in motor-network structure and function. Resting-state and transcranial magnetic stimulation-evoked electroencephalography revealed brain functional changes, and magnetic resonance imaging (MRI) measures detected structural and task-related functional changes.
These first results are promising, pointing to feasibility, safety, and potential efficacy of this personalized approach acting synergistically on the nervous and musculoskeletal systems. Integrating multi-modal data may provide valuable insights into underlying mechanisms driving the improvements and providing predictive information regarding treatment response and outcomes.
This work was funded by the Wyss-Center for Bio and Neuro Engineering (WCP-030), the Defitech Foundation, PHRT-#2017-205, ERA-NET-NEURON (Discover), and SNSF (320030L_197899, NiBS-iCog).
大约 25%的中风患者存在严重的上肢功能障碍，且缺乏有效的康复策略。AVANCER 概念验证临床试验（NCT04448483）通过结合多种非侵入性神经技术的强化和个性化剂量累积干预来解决这个问题。
该治疗包括两个连续的干预阶段，持续到患者不再有进一步的运动改善，每个阶段至少进行 11 次。第一阶段包括一个控制外骨骼和多通道功能性电刺激的脑机接口，以实现全上肢运动。第二阶段增加了对病灶半球运动皮层的阳极经颅直流电刺激。在两次干预之前（T0）、之间（T1）和之后（T2）进行临床、电生理和神经影像学检查。本病例报告介绍了该研究的第一个患者的结果。
第一个患者的主要结局（即上肢 Fugl-Meyer 评估提高 4 分）得到了满足，从 T0 到 T2 从 6 分增加到 11 分。这种改善与运动网络结构和功能的变化相平行。静息状态和经颅磁刺激诱发的脑电图显示大脑功能发生变化，磁共振成像（MRI）测量则检测到结构和与任务相关的功能变化。
这些初步结果令人鼓舞，表明这种针对神经和肌肉骨骼系统的个性化方法具有可行性、安全性和潜在疗效，其协同作用。整合多模态数据可能为驱动改善的潜在机制提供有价值的见解，并提供有关治疗反应和结果的预测信息。
这项工作得到了 Wyss 生物与神经工程中心（WCP-030）、Defitech 基金会、PHRT-#2017-205、欧洲研究区神经技术网络（Discover）和瑞士国家科学基金会（320030L_197899、NiBS-iCog）的资助。
