Assessment of EEG Responses to Spinal Cord Stimulation Waveforms in Chronic Pain Patients

慢性疼痛患者对脊髓刺激波形的脑电图反应评估

• 批准号: 10321562
• 负责人: Ilknur Telkes Ergun
• 金额: $ 2.09万
• 依托单位: ALBANY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10321562
• 关键词: Achievement; Adult; Advanced Development; Affect; Affective; Alpha Rhythm; American; Beck depression inventory; Biological Markers; Brain; Brain region; Chronic; Clinical; Complex; Conscious; Consensus; Custom; Data; Decision Making; Development; Devices; Economic Burden; Electroencephalography; Esthesia; Frequencies; Future; Goals; Health Expenditures; Healthcare; Hour; Implant; Individual; Intractable Pain; Intraoperative Monitoring; Lead; Link; McGill Pain Scale; Measurement; Measures; Medical; Methodology; Neurostimulation procedures of spinal cord tissue; Numbness; Numeric Rating Scale; Operative Surgical Procedures; Outcome; Outcome Measure; Pain; Pain Measurement; Paresthesia; Patient Self-Report; Patients; Pattern; Persons; Pharmaceutical Preparations; Physiologic pulse; Physiological; Postoperative Period; Refractory; Reporting; Rest; Scanning; Sensory; Shapes; Sleep; Spatial Distribution; Therapeutic; Training; United States Food and Drug Administration; Work; awake; base; chronic neuropathic pain; chronic pain; chronic pain management; chronic pain patient; chronic painful condition; clinical efficacy; clinical risk; cost; disability; efficacy study; experience; implantation; improved; insight; mathematical model; meetings; neural correlate; neural patterning; neurophysiology; neuroregulation; neurotechnology; non-opioid analgesic; novel; pain catastrophizing; pain relief; pain sensation; patient subsets; productivity loss; relating to nervous system; response; sensory gating; somatosensory; success; temporal measurement; tool; treatment response

Chronic pain is a significant problem and it has been estimated to affect about 50 million adult Americans. It accounts for more than 600 billion dollars in health care expenditures, disability and loss of productivity and remains one of the most common reasons that patients seek healthcare. Spinal cord stimulation (SCS) is a Food and Drug Administration (FDA)-approved neuromodulation treatment to relieve chronic refractory pain. While SCS can be used effectively in many patients with refractory chronic pain conditions, a significant portion of the patients receive suboptimal or inadequate pain suppression. Considering that over 30,000 individuals receive SCS implantation on an annual basis for chronic pain and an annual cost of over $24,000 per patient resulting from lack of satisfactory pain relief due to lack of consensus regarding optimal stimulation parameters, it is crucial to improve the clinical efficacy of SCS in chronic refractory pain. Beside the traditional stimulation (tonic), using novel stimulation waveforms such as burst and high frequency stimulation (HFS) is one approach. These waveforms do not induce paresthesia (sensation of tingling or numbness) and their effects are often delayed 24- 48 hours unlike tonic stimulation, where the effects are immediate. However, the supraspinal effects of these waveforms are still not very clear. It is also unknown why some patients respond well to one waveform over another. Another limitation is that assessment of the pain relief by SCS depends almost exclusively on patient self-reports and lack of objective measurements of SCS implants results might lead to increased number of failed permanent placements. In this regard, investigating neural patterns of SCS waveforms and assess SCS-induced pain relief by using electroencephalography (EEG) in awake and anesthetized chronic pain patients appears essential. Our preliminary data suggests that changes in alpha peak frequency and ratio of alpha and theta band power might be correlated to SCS-induced pain relief. The spatial distribution of these patterns is closely related to which waveform is used. We hypothesize that intra-operative EEG demonstrates similar spatio-spectral patterns to post-operative EEG. We predict that pain relief will correlate best with increased alpha band power in frontal and somatosensory regions in burst stimulation and somatosensory cortical regions in HFS. In this proposal, our objectives are to determine the relationship between alpha band features and SCS-induced pain relief in awake patients (Aim 1), determine the spatio-spectral differences between “sleep” and awake states EEG and characterize the intra-operative neural correlates of pain relief (Aim 2), and examine the changes in alpha band features when patients with minimal pain relief are reprogrammed to experience pain relief (Aim 3). Specifically, in Aim 3, we will develop a mathematical model based on these neural features and patients will be temporarily programmed to this EEG-guided setting. We will investigate the predictive power of the assessed neural patterns on selection of the optimal waveform. The immediate goal of this project is to develop quantified, neural signatures of pain relief. These objective markers could form an objective metric for device selection, which might reduce the healthcare expenditures associated with failed implants and help in guiding SCS parameters for better pain relief, especially in patients with minimal pain relief. Overall, these objective neurophysiological measures can be used for more personalized SCS therapy with higher efficacy, and, this study can contribute to development of neurotechnologies and neuroengineering methodologies.

慢性疼痛是一个重大的问题，据估计会影响约5000万成年美国人。它占医疗保健支出，残疾和生产力损失的6000亿美元，仍然是患者寻求医疗保健的最常见原因之一。脊髓刺激（SCS）是食品药物管理（FDA）批准的神经调节治疗，可挽救慢性难治性疼痛。虽然可以使用SC，但考虑到30,000多人每年接受SC植入慢性疼痛，并且由于缺乏满意设施减轻疼痛而导致的每名患者的年费用超过24,000美元，因此在最佳刺激参数方面缺乏共识，这对于提高SCS临床效率的慢性逆性疼痛至关重要。除了传统刺激（补品）外，使用新型刺激波形（例如爆发和高频刺激（HFS））是一种方法。这些波形不会诱导寄生虫（刺痛或麻木的感觉），并且与滋补刺激不同，其影响通常会延迟24-48小时，而这种刺激立即效果。但是，这些波形的上脊髓效应仍然不太清楚。尚不清楚为什么有些患者对一个波形在另一个波形上反应良好。另一个局限性是，SC对SC的缓解的评估几乎完全取决于患者的自我报告，而缺乏对SCS的客观测量结果可能会导致永久性位置失败的数量增加。在这方面，通过在清醒和麻醉慢性疼痛患者中使用脑电图（EEG）来研究SCS波形的中性模式和评估SCS诱导的疼痛缓解。我们的初步数据表明，α峰频率的变化和α和theta带功率的比率可能与SCS诱导的疼痛缓解相关。这些模式的空间分布与使用的波形密切相关。我们假设术中脑电图与术后脑电图相似。我们预测，缓解疼痛将与HFS的爆发刺激和体感皮质区域中额叶和体感区域的α频带功率提高相关。 In this proposal, our objectives are to determine the relationship between alpha band features and SCS-induced pain relief in awake patients (Aim 1), determine the spatial-spectral differences between “sleep” and awake states EEG and characterize the intra-operative neural correlates of pain relief (Aim 2), and examine the changes in alpha band features when patients with minimal pain relief are reprogrammed to experience pain relief (Aim 3).Specifically,在AIM 3中，我们将开发基于这些神经元特征的数学模型，患者将临时编程为EEG引导的环境。我们将研究评估的神经元模式的预测能力，以选择最佳波形。该项目的直接目标是开发量化疼痛的量化神经特征。这些客观标记可能会成为设备选择的客观指标，这可能会减少与失败的医疗支出相关的医疗支出，并有助于指导SCS参数，以改善疼痛，尤其是在减轻疼痛的患者中。总体而言，这些客观的神经生理学指标可用于具有更高效率的更个性化的SC疗法，并且这项研究可以有助于神经技术和神经工程方法的发展。

项目成果

Patient-specific modeling of the volume of tissue activated (VTA) is associated with clinical outcome of DBS in patients with an obsessive-compulsive disorder.

• DOI: 10.1109/embc46164.2021.9630273
• 发表时间: 2021-11
• 期刊: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

Development of Machine Learning-Based Models to Predict Treatment Response to Spinal Cord Stimulation.

开发基于机器学习的模型来预测对脊髓刺激的治疗反应。

• DOI: 10.1227/neu.0000000000001855
• 发表时间: 2022
• 期刊: Neurosurgery
• 影响因子: 4.8
• 作者: Hadanny,Amir;Harland,Tessa;Khazen,Olga;DiMarzio,Marisa;Marchese,Anthony;Telkes,Ilknur;Sukul,Vishad;Pilitsis,JulieG
• 通讯作者: Pilitsis,JulieG

In Reply: Development of Machine Learning-Based Models to Predict Treatment Response to Spinal Cord Stimulation.

回复：开发基于机器学习的模型来预测对脊髓刺激的治疗反应。

• DOI: 10.1227/neu.0000000000002047
• 发表时间: 2022
• 期刊: Neurosurgery
• 影响因子: 4.8
• 作者: Hadanny,Amir;Harland,TessaA;Khazen,Olga;DiMarzio,Marisa;Telkes,Ilknur;Pilitsis,JulieG
• 通讯作者: Pilitsis,JulieG