Lam Danny V, Chin Justin, Brucker-Hahn Meagan K, Settell Megan, Romanauski Ben, Verma Nishant, Upadhye Aniruddha, Deshmukh Ashlesha, Skubal Aaron, Nishiyama Yuichiro, Hao Jian, Lujan J Luis, Zhang Simeng, Knudsen Bruce, Blanz Stephan, Lempka Scott F, Ludwig Kip A, Shoffstall Andrew J, Park Hyun-Joo, Ellison Erika Ross, Zhang Mingming, Lavrov Igor
Neural Lab, Abbott Neuromodulation, Plano, TX, USA.
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
Bioelectron Med. 2024 Jul 17;10(1):17. doi: 10.1186/s42234-024-00149-2.
Spinal cord stimulation (SCS) has demonstrated multiple benefits in treating chronic pain and other clinical disorders related to sensorimotor dysfunctions. However, the underlying mechanisms are still not fully understood, including how electrode placement in relation to the spinal cord neuroanatomy influences epidural spinal recordings (ESRs). To characterize this relationship, this study utilized stimulation applied at various anatomical sections of the spinal column, including at levels of the intervertebral disc and regions correlating to the dorsal root entry zone.
Two electrode arrays were surgically implanted into the dorsal epidural space of the swine. The stimulation leads were positioned such that the caudal-most electrode contact was at the level of a thoracic intervertebral segment. Intraoperative cone beam computed tomography (CBCT) images were utilized to precisely determine the location of the epidural leads relative to the spinal column. High-resolution microCT imaging and 3D-model reconstructions of the explanted spinal cord illustrated precise positioning and dimensions of the epidural leads in relation to the surrounding neuroanatomy, including the spinal rootlets of the dorsal and ventral columns of the spinal cord. In a separate swine cohort, implanted epidural leads were used for SCS and recording evoked ESRs.
Reconstructed 3D-models of the swine spinal cord with epidural lead implants demonstrated considerable distinctions in the dimensions of a single electrode contact on a standard industry epidural stimulation lead compared to dorsal rootlets at the dorsal root entry zone (DREZ). At the intervertebral segment, it was observed that a single electrode contact may cover 20-25% of the DREZ if positioned laterally. Electrode contacts were estimated to be ~0.75 mm from the margins of the DREZ when placed at the midline. Furthermore, ventral rootlets were observed to travel in proximity and parallel to dorsal rootlets at this level prior to separation into their respective sides of the spinal cord. Cathodic stimulation at the level of the intervertebral disc, compared to an 'off-disc' stimulation (7 mm rostral), demonstrated considerable variations in the features of recorded ESRs, such as amplitude and shape, and evoked unintended motor activation at lower stimulation thresholds. This substantial change may be due to the influence of nearby ventral roots. To further illustrate the influence of rootlet activation vs. dorsal column activation, the stimulation lead was displaced laterally at ~2.88 mm from the midline, resulting in variances in both evoked compound action potential (ECAP) components and electromyography (EMG) components in ESRs at lower stimulation thresholds.
The results of this study suggest that the ECAP and EMG components of recorded ESRs can vary depending on small differences in the location of the stimulating electrodes within the spinal anatomy, such as at the level of the intervertebral segment. Furthermore, the effects of sub-centimeter lateral displacement of the stimulation lead from the midline, leading to significant changes in electrophysiological metrics. The results of this pilot study reveal the importance of the small displacement of the electrodes that can cause significant changes to evoked responses SCS. These results may provide further valuable insights into the underlying mechanisms and assist in optimizing future SCS-related applications.
脊髓刺激(SCS)已在治疗慢性疼痛及其他与感觉运动功能障碍相关的临床疾病中展现出多种益处。然而,其潜在机制仍未完全明晰,包括电极相对于脊髓神经解剖结构的放置方式如何影响硬膜外脊髓记录(ESR)。为了明确这种关系,本研究在脊柱的不同解剖节段施加刺激,包括椎间盘水平以及与背根入区相关的区域。
将两个电极阵列手术植入猪的硬膜外间隙。刺激导线的放置方式使得最尾端的电极触点位于胸段椎间节段水平。术中利用锥形束计算机断层扫描(CBCT)图像精确确定硬膜外导线相对于脊柱的位置。对取出的脊髓进行高分辨率微计算机断层扫描(microCT)成像和三维(3D)模型重建,以阐明硬膜外导线相对于周围神经解剖结构(包括脊髓背侧和腹侧柱的神经根丝)的精确定位和尺寸。在另一组猪中,植入的硬膜外导线用于SCS并记录诱发的ESR。
带有硬膜外导线植入物的猪脊髓3D重建模型显示,与背根入区(DREZ)的背侧神经根丝相比,标准工业硬膜外刺激导线上单个电极触点的尺寸存在显著差异。在椎间节段观察到,如果将单个电极触点放置在外侧,它可能覆盖DREZ的20 - 25%。当放置在中线时,电极触点估计距离DREZ边缘约0.75毫米。此外,在此水平观察到腹侧神经根丝在分离到脊髓各自一侧之前,靠近并平行于背侧神经根丝走行。与“离盘”刺激(头端7毫米)相比,在椎间盘水平进行阴极刺激时,记录的ESR特征(如幅度和形状)有显著差异,并且在较低刺激阈值下诱发了意外的运动激活。这种显著变化可能是由于附近腹侧神经根丝的影响。为了进一步说明神经根丝激活与背侧柱激活的影响,将刺激导线从中线横向移位约2.88毫米,导致在较低刺激阈值下ESR中诱发的复合动作电位(ECAP)成分和肌电图(EMG)成分均出现变化。
本研究结果表明,记录的ESR中的ECAP和EMG成分可能会因刺激电极在脊髓解剖结构内位置的微小差异(如在椎间节段水平)而有所不同。此外,刺激导线从中线进行亚厘米级的横向移位会导致电生理指标发生显著变化。这项初步研究的结果揭示了电极的微小移位对SCS诱发反应产生显著变化的重要性。这些结果可能为潜在机制提供进一步有价值的见解,并有助于优化未来与SCS相关的应用。