Closed-loop Spinal Cord Stimulation Research Articles

Network Meta-analysis and Economic Evaluation of Neurostimulation Interventions for Chronic Non-surgical Refractory back Pain.

Different types of spinal cord stimulation (SCS) have now been evaluated for the management of chronic non-surgical refractory back pain (NSRBP). A direct comparison between the different types of SCS or between closed-loop SCS with conventional medical management (CMM) for patients with NSRBP has not been previously conducted, and therefore, their relative effectiveness and cost-effectiveness remain unknown. The aim of this study was to perform a systematic review, network meta-analysis (NMA) and economic evaluation of closed-loop SCS compared with fixed-output SCS and CMM for patients with NSRBP. Databases were searched to 8th September 2023. Randomised controlled trials of SCS for NSRBP were included. Results of studies were combined using fixed-effect NMA models. A cost-utility analysis was performed from the perspective of the UK National Health Service with results reported as incremental cost per quality-adjusted life-year (QALY). Closed-loop SCS resulted in statistically and clinically significant reductions in pain intensity (mean difference [MD] 32.72 [95% CrI 15.69-49.78]) and improvements in secondary outcomes compared to fixed-output SCS at 6-months follow-up. Compared to CMM, both closed-loop and fixed-output SCS result in statistically and clinically significant reductions in pain intensity (closed-loop SCS vs. CMM MD 101.58 [95% CrI 83.73-119.48]; fixed-output SCS versus CMM MD 68.86 [95% CrI 63.43-74.31]) and improvements in secondary outcomes. Cost-utility analysis shows that closed-loop SCS dominates fixed-output SCS and CMM, and fixed-output SCS also dominates CMM. Current evidence shows that closed-loop and fixed-output SCS provide more benefits and are cost-saving compared to CMM for patients with NSRBP.

Outcomes of ECAP-controlled closed-loop spinal cord stimulation therapy in JAPAN: how to increase patient satisfaction with spinal cord stimulation

Objective: Orthopedic surgeons commonly encounter patients with low back pain and leg pain. Despite conservative treatment, which may involve the use of weak opioids or NSAIDs, some patients do not experience improvement and may require increased dosages, contributing to concerns about opioid overuse overseas. Spinal cord stimulation (SCS) therapy, which can be trialed without surgical intervention, offers a potential treatment option. We evaluated Inceptiv (Medtronic), a generator that allows new stimulation settings using evoked compound action potentials (ECAPs)-controlled Closed-Loop technology. Methods: We evaluated six patients (four females, two males) who underwent implantation of the Inceptiv generator for SCS therapy. The average walking time (seconds) during a 2.1-meter walk and pain assessment using the Numerical Rating Scale (NRS) were conducted. Patient satisfaction was assessed using a 5-point scale: very satisfied (5), somewhat satisfied (4), neutral (3), somewhat dissatisfied (2), very dissatisfied. (1). Results: The average walking time improved from 11.8 seconds to 6.6 seconds, and the NRS score decreased from 7.6 to 4.2. Patient satisfaction was high, with four patients being very satisfied (5), one somewhat satisfied (4), and one neutral (3). Discussion: SCS therapy with Closed-Loop technology using the Inceptiv generator offers the potential to adjust electrical stimulation to minimize discomfort in daily activities and provide pain relief. It is considered a new treatment option for patients with common orthopedic conditions such as thoracolumbar compression fractures and lumbar spinal stenosis who suffer from chronic refractory pain in routine clinical practice.

First evidence of a biomarker-based dose-response relationship in chronic pain using physiological closed-loop spinal cord stimulation

Background and objectivesIn spinal cord stimulation (SCS) therapy, electricity is the medication delivered to the spinal cord for pain relief. In contrast to conventional medication where dose is determined by...

Neurophysiological outcomes that sustained clinically significant improvements over 3 years of physiologic ECAP-controlled closed-loop spinal cord stimulation for the treatment of chronic pain

IntroductionA novel, spinal cord stimulation (SCS) system with a physiologic closed-loop (CL) feedback mechanism controlled by evoked compound action potentials (ECAPs) enables the optimization of physiologic neural dose and the...

Evoked compound action potential (ECAP)-controlled closed-loop spinal cord stimulation in an experimental model of neuropathic pain in rats

BackgroundPreclinical models of spinal cord stimulation (SCS) are lacking objective measurements to inform translationally applicable SCS parameters. The evoked compound action potential (ECAP) represents a measure of dorsal column fiber activation. This measure approximates the onset of SCS-induced sensations in humans and provides effective analgesia when used with ECAP-controlled closed-loop (CL)-SCS systems. Therefore, ECAPs may provide an objective surrogate for SCS dose in preclinical models that may support better understanding of SCS mechanisms and further translations to the clinics. This study assessed, for the first time, the feasibility of recording ECAPs and applying ECAP-controlled CL-SCS in freely behaving rats subjected to an experimental model of neuropathic pain.MethodsAdult male Sprague–Dawley rats (200–300 g) were subjected to spared nerve injury (SNI). A custom-made six-contact lead was implanted epidurally covering T11-L3, as confirmed by computed tomography or X-ray. A specially designed multi-channel system was used to record ECAPs and to apply ECAP-controlled CL-SCS for 30 min at 50 Hz 200 µs. The responses of dorsal column fibers to SCS were characterized and sensitivity towards mechanical and cold stimuli were assessed to determine analgesic effects from ECAP-controlled CL-SCS. Comparisons between SNI rats and their controls as well as between stimulation parameters were made using omnibus analysis of variance (ANOVA) tests and t-tests.ResultsThe recorded ECAPs showed the characteristic triphasic morphology and the ECAP amplitude (mV) increased as higher currents (mA) were applied in both SNI animals and controls (SNI SCS-ON and sham SCS-ON). Importantly, the use of ECAP-based SCS dose, implemented in ECAP-controlled CL-SCS, significantly reduced mechanical and cold hypersensitivity in SNI SCS-ON animals through the constant and controlled activation of dorsal column fibers. An analysis of conduction velocities of the evoked signals confirmed the involvement of large, myelinated fibers.ConclusionsThe use of ECAP-based SCS dose implemented in ECAP-controlled CL-SCS produced analgesia in animals subjected to an experimental model of neuropathic pain. This approach may offer a better method for translating SCS parameters between species that will improve understanding of the mechanisms of SCS action to further advance future clinical applications.

Restoration of sensory feedback from the foot and reduction of phantom limb pain via closed-loop spinal cord stimulation

Restoration of sensory feedback from the foot and reduction of phantom limb pain via closed-loop spinal cord stimulation

Device profile of the Evoke physiologic closed-loop spinal cord stimulation system for the treatment of chronic intractable pain: overview of its safety and efficacy

ABSTRACT Introduction The Evoke® spinal cord stimulation (SCS) device enables the closed-loop feedback of dynamically measured evoked compound action potentials (ECAPs) to adjust stimulation amplitude for every stimulation pulse to maintain the stimulation output level near a targeted ECAP amplitude. No other commercially available SCS device presently uses physiologic feedback from the spinal cord to adjust stimulation. Clinicians should be familiar with the differences in devices and with the latest technologies to provide optimized patient care. Areas covered In this device profile, the Evoke system is described and the system capabilities are differentiated from other available SCS devices. A systematic review was conducted based on best practice guidance to identify all available evidence on the safety and efficacy of the Evoke SCS system. Expert opinion The Evoke SCS system offers unique capabilities as a means to optimize therapy delivery tailored to each individual patient. Data through 24-months follow-up show statistically significant, clinically meaningful, ample, consistent, and strong evidence of the safety and efficacy of the Evoke system for the treatment of chronic intractable pain.

ECAP-controlled closed-loop versus open-loop SCS for the treatment of chronic pain: 36-month results of the EVOKE blinded randomized clinical trial

IntroductionThe evidence for spinal cord stimulation (SCS) has been criticized for the absence of blinded, parallel randomized controlled trials (RCTs) and limited evaluations of the long-term effects of SCS in...

Durable multimodal and holistic response for physiologic closed-loop spinal cord stimulation supported by objective evidence from the EVOKE double-blind randomized controlled trial

IntroductionChronic pain patients may experience impairments in multiple health-related domains. The design and interpretation of clinical trials of chronic pain interventions, however, remains primarily focused on treatment effects on pain...

First Report on Real-World Outcomes with Evoked Compound Action Potential (ECAP)-Controlled Closed-Loop Spinal Cord Stimulation for Treatment of Chronic Pain.

A novel closed-loop spinal cord stimulation (SCS) system has recently been approved for use which records evoked compound action potentials (ECAPs) from the spinal cord and utilizes these recordings to automatically adjust the stimulation strength in real time. It automatically compensates for fluctuations in distance between the epidural leads and the spinal cord by maintaining the neural response (ECAP) at a determined target level. This data collection was principally designed to evaluate the performance of this first closed-loop SCS system in a 'real-world' setting under normal conditions of use in a single European center. In this prospective, single-center observational data collection, 22 patients were recruited at the outpatient pain clinic of the St. Antonius Hospital. All candidates were suffering from chronic pain in the trunk and/or limbs due to PSPS type 2 (persistent spinal pain syndrome). As standard of care, follow-up visits were completed at 3months, 6months, and 12months post-device activation. Patient-reported outcome data (pain intensity, patient satisfaction) and electrophysiological and device data (ECAP amplitude, conduction velocity, current output, pulse width, frequency, usage), and patient interaction with their controller were collected at baseline and during standard of care follow-up visits. Significant decreases in pain intensity for overall back or leg pain scores (verbal numerical rating score=VNRS) were observed between baseline [mean±SEM (standard error of the mean); n=22; 8.4±0.2)], 3months (n=12; 1.9±0.5), 6months (n=16; 2.6±0.5), and 12months (n=20; 2.0±0.5), with 85.0% of the patients being satisfied at 12months. Additionally, no significant differences in average pain relief at 3months and 12months between the real-world data (77.2%; 76.8%) and the AVALON (71.2%; 73.6%) and EVOKE (78.1%; 76.7%) studies were observed. These initial 'real-world' data on ECAP-controlled, closed-loop SCS in a real-world clinical setting appear to be promising, as they provide novel insights of the beneficial effect of ECAP-controlled, closed-loop SCS in a real-world setting. The presented results demonstrate a noteworthy maintenance of pain relief over 12months and corroborate the outcomes observed in the AVALON prospective, multicenter, single-arm study and the EVOKE double-blind, multicenter, randomized controlled trial. The data collection is registered on the International Clinical Trials Registry Platform (Trial NL7889).

ID: 210553 Clinical Feasibility of ECAP-Controlled, Closed-Loop Spinal Cord Stimulation With Cervically Placed Leads

Recent advances in spinal cord stimulation (SCS) have focused on two highly novel areas; Differential Target MultiplexedTM SCS (DTM) [1], which has demonstrated superior pain relief, and the spinal Evoked Compound Action Potential (ECAP), a bioelectrical signal used as a measure of neural activation with closed-loop (CL) SCS systems to compensate for motion at the electrode-tissue interface [2]. Due to thinner cerebral spinal fluid (CSF) and the large mobility in the cervical space compared to the thoracic space [3], the use of ECAP-controlled SCS systems for upper limb pain may reduce uncomfortable stimulation delivered to patients and decrease the variation in stimulation delivered to the cord. In this study, ECAP-controlled closed-loop DTMTM SCS was explored to assess feasibility with cervically placed SCS leads in an in-clinic environment.

ID: 214925 Early Experience With Closed-Loop SCS During In-Clinic Testing

Therapeutic outcomes with spinal cord stimulation (SCS) have continued to improve with the introduction of new waveforms.1 However, regardless of the waveform in use, the therapy dose delivered to the cord will vary dynamically due to the movement of the cord within the spinal canal, relative to the SCS lead. This leads to the activation of different volumes of tissue and inconsistent therapy delivery. Patients typically respond by adjusting the therapy amplitude up or down, which could result in less-than-optimal pain relief.2 Closed-Loop SCS, titrated by the physiologic response of the spinal cord to stimulation – known as evoked compound action potential (ECAPs), can be used to effectively mitigate this issue and maintain a consistent therapeutic dose.3 The objective of this study is to optimize a workflow to efficiently program Closed-Loop SCS with contemporary waveforms (e.g., Differential Target Multiplexed (DTM) SCS), with an investigational external neurostimulator (ENS), capable of stimulating and recording ECAPs, in Medtronic SCS trial participants.

ID: 208638 Evoked Compound Action Potentials and Closed-Loop Spinal Cord Stimulation in Neuropathic Rats: Feasibility Study

Evoked compound action potentials (ECAPs) identified during spinal cord stimulation (SCS) in humans have been observed to closely correlate with the activation of the stimulation-induced sensory perception perceived as paresthesia1. We recently demonstrated feasibility of recording ECAPs from the spinal cord in naïve rats using uniquely designed equipment2. Here, we extended our experiments to provide electrophysiological characteristics of the response of dorsal column axons to SCS based on ECAPs recording in rats with neuropathic pain. Moreover, we demonstrate the ability to deliver ECAP-controlled closed-loop SCS in neuropathic pain rats, which has been proven superior to open-loop stimulation in humans3,4.

ID: 211562 Real-World Treatment Outcomes With ECAP-Controlled Closed-Loop Spinal Cord Stimulation: The Dutch Triangle Pain Clinic Experience

Evoked Compound Action Potential (ECAP)-controlled closed-loop spinal cord stimulation (SCS) measures and controls neural activation in real-time. Consistent and accurate neural activation resulted in superior pain relief in closed-loop compared to traditional, open-loop SCS patients [1],[2]. Here, interim results from 3 Dutch clinics (Triangle Painclinics) are presented (Netherlands Trial Register, ID: NL7889; NL9392).

ID: 208554 Real-World Preliminary Data of ECAP-Controlled Closed-Loop SCS Closely Match With Results of More Controlled Studies

Spinal cord stimulation (SCS) has proven to be an effective therapy for chronic pain [1], [2]. A randomized-controlled-trial (RCT) and a long-term open label multi-center-study indicate that Evoked Compound Action Potential (ECAP)-controlled closed-loop SCS demonstrated more consistent activation of the spinal cord and correspondingly superior pain relief in patients as compared to traditional ‘open-loop’ SCS [3], [5]. Results from RCT studies are sometimes hard to repeat in real-world. Here, interim real-world results of the multi-center data collection study (Data Release) from seven centers in the Netherlands are presented (Netherlands Trial Register, ID: NL7889).

ID: 215136 Inter-Patient Variability in the Evoked Compound Action Potentials Generated During Spinal Cord Stimulation

A paresthesia-centric closed-loop spinal cord stimulation (SCS) system described recently uses evoked compound action potentials (ECAPs) as a control signal to compensate for spinal cord movement [1]. While ECAP-based SCS has demonstrated clinical efficacy, significant knowledge gaps remain about how the main control variable (i.e., ECAP amplitude) and other metrics (e.g., ECAP threshold (ET), ECAP growth rate) vary across subjects, postures, and pulse widths. These knowledge gaps may complicate the appropriate application of ECAP-controlled, closed-loop SCS. Therefore, in this study, we utilized a combined experimental and computational modeling approach to answer these questions.

ID: 213534 Early Outcomes With the Medtronic Closed-Loop Spinal Cord Stimulation Study

Spinal cord stimulation (SCS) is a therapy for the treatment of chronic pain that relies on the application of mild electrical stimulation delivered to the dorsal column fibers of the spinal cord via lead(s) implanted in the epidural space. Most of the current SCS systems do not adjust the stimulation to reflect changes in distance between the SCS lead and the cord during activities of daily living. Hence, the net energy delivered varies dynamically resulting in inconsistent therapy delivery i.e., open-loop (OL) SCS.1 Closed-Loop SCS (CL SCS), where the therapy is titrated by the physiologic response of the spinal cord to stimulation – known as evoked compound action potential (ECAPs),2 can be used to address this limitation of OL SCS systems. The objective of this study is to evaluate patient experience and therapy durability with CL SCS. Primary study objective is to demonstrate the reduction in overstimulation sensation with the CL feature in subjects implanted with the CL SCS system. Secondary objectives include characterizing therapy efficacy in reducing overall, back or leg pain as measured by the proportion of subjects with ≥50% reduction in pain score, at the time of the 3-month visit. Consistency of dosing and long-term durability of therapy will also be characterized.

ID: 210803 High-Resolution-Doppler-Ultrasound as an Objective Outcome Parameter of ECAP-Controlled Closed-Loop SCS in Patients With Raynaud Phenomenon

Raynaud's phenomenon (RP) is an episodically occurring vasospasm of the peripheral arteries that causes cyanosis, erythema, pain, paresthesia, and sometimes ulceration of the fingers and/or toes [1]. In severe cases, RP patients have physical and functional impairments that substantially affect their ability to work. There are few reports, mostly case series, on the utility of spinal cord stimulation (SCS) to treat RP [2]–[9]. However, there is a lack of objective evidence on the physiological effects (e.g., vasodilation) of SCS in this condition. Here, we present clinical outcomes of severe RP patients treated with evoked compound action potential (ECAP)-controlled closed-loop SCS.

ID: 215794 ECAP-Based SCS for the Treatment of Chronic Pain: Crossover and 36-Month Evoke Study Outcomes

Utilization of objective neurophysiological measures to guide clinicians in providing optimal spinal cord stimulation (SCS) for chronic pain patients is a novel concept to neuromodulation. This clear and transparent mechanistic approach provides a better understanding to clinicians, patients, and payors allowing for proper evaluation of clinical outcomes. A novel SCS system delivers evoked-compound action potentials (ECAPs)-based therapy to 1) Guide programming and confirm activation of the intended target (i.e., ECAP-guided programming); and 2) Deliver closed-loop therapy to maintain accurate and consistent neural activation on every stimulus (i.e., ECAP-controlled closed-loop SCS). This therapy has now been studied in a 24-month double-blind randomized controlled trial (RCT) with self-selected crossover through 36 months. ECAP-based therapy enables real-time collection of continuous, objective, in-vivo neurophysiological data. This provides proper evaluation of the therapy and interpretation of the clinical outcomes, resulting in a level of evidence unmatched in neuromodulation.

ID: 222629 ECAP Study: Evaluating Holistic Response & Neurophysiology in Real-World Chronic Pain Using ECAP-Controlled Closed-Loop SCS

Chronic pain is a complex and personal experience influenced to varying degrees by biopsychosocial factors.1 Although several of these factors are commonly investigated in clinical trials, treatment response to interventions such as spinal cord stimulation (SCS) has often been based solely on reported reduction in pain intensity. As neurostimulation technology advances and substantial reductions in pain intensity are more commonly observed, the pursuit for a holistic responder beyond pain intensity alone has gained increased interest.2-5 This study aims to characterize the holistic treatment response of a real-world chronic pain population utilizing ECAP-controlled closed-loop SCS and explore the association with objective neurophysiological measurements.