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

INTRODUCTION: The 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 RCTs. The aim of this study was to determine whether evoked compound action potential (ECAP)-controlled, closed-loop SCS (CL-SCS) is associated with better outcomes when compared with fixed-output, open-loop SCS (OL-SCS) 36 months following implant. METHODS: The EVOKE study was a multicenter, participant-blinded, investigator-blinded, and outcome assessor-blinded, randomized, controlled, parallel-arm clinical trial that compared ECAP-controlled CL-SCS with fixed-output OL-SCS. Participants with chronic, intractable back and leg pain refractory to conservative therapy were enrolled between January 2017 and February 2018, with follow-up through 36 months. The primary outcome was a reduction of at least 50% in overall back and leg pain. Holistic treatment response, a composite outcome including pain intensity, physical and emotional functioning, sleep, and health-related quality of life, and objective neural activation was also assessed. RESULTS: At 36 months, more CL-SCS than OL-SCS participants reported ≥50% reduction (CL-SCS=77.6%, OL-SCS=49.3%; difference: 28.4%, 95% CI 12.8% to 43.9%, p<0.001) and ≥80% reduction (CL-SCS=49.3%, OL-SCS=31.3%; difference: 17.9, 95% CI 1.6% to 34.2%, p=0.032) in overall back and leg pain intensity. Clinically meaningful improvements from baseline were observed at 36 months in both CL-SCS and OL-SCS groups in all other patient-reported outcomes with greater levels of improvement with CL-SCS. A greater proportion of patients with CL-SCS were holistic treatment responders at 36-month follow-up (44.8% vs 28.4%), with a greater cumulative responder score for CL-SCS patients. Greater neural activation and accuracy were observed with CL-SCS. There were no differences between CL-SCS and OL-SCS groups in adverse events. No explants due to loss of efficacy were observed in the CL-SCS group. CONCLUSION: This long-term evaluation with objective measurement of SCS therapy demonstrated that ECAP-controlled CL-SCS resulted in sustained, durable pain relief and superior holistic treatment response through 36 months. Greater neural activation and increased accuracy of therapy delivery were observed with ECAP-controlled CL-SCS than OL-SCS. TRIAL REGISTRATION NUMBER: NCT02924129.

The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations on Best Practices for Cervical Neurostimulation.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise with international representation to establish evidence-based guidance on the use of neurostimulation in the cervical region to improve outcomes. This Neurostimulation Appropriateness Consensus Committee (NACC) project intends to provide evidence-based guidance for an often-overlooked area of neurostimulation practice. MATERIALS AND METHODS: Authors were chosen based upon their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when NACC last published guidelines) to the present. Identified studies were graded using the US Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence was scant. RESULTS: The NACC examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The NACC recommends best practices regarding the use of cervical neuromodulation to improve safety and efficacy. The evidence- and consensus-based recommendations should be utilized as a guide to assist decision making when clinically appropriate.

Treatment of chronic axial back pain with 60-day percutaneous medial branch PNS: Primary end point results from a prospective, multicenter study.

BACKGROUND: The objective of this prospective, multicenter study is to characterize responses to percutaneous medial branch peripheral nerve stimulation (PNS) to determine if results from earlier, smaller single-center studies and reports were generalizable when performed at a larger number and wider variety of centers in patients recalcitrant to nonsurgical treatments. MATERIALS & METHODS: Participants with chronic axial low back pain (LBP) were implanted with percutaneous PNS leads targeting the lumbar medial branch nerves for up to 60 days, after which the leads were removed. Participants were followed long-term for 12 months after the 2-month PNS treatment. Data collection is complete for visits through end of treatment with PNS (primary end point) and 6 months after lead removal (8 months after start of treatment), with some participant follow-up visits thereafter in progress. RESULTS: Clinically and statistically significant reductions in pain intensity, disability, and pain interference were reported by a majority of participants. Seventy-three percent of participants were successes for the primary end point, reporting clinically significant (≥30%) reductions in back pain intensity after the 2-month percutaneous PNS treatment (n = 54/74). Whereas prospective follow-up is ongoing, among those who had already completed the long-term follow-up visits (n = 51), reductions in pain intensity, disability, and pain interference were sustained in a majority of participants through 14 months after the start of treatment. CONCLUSION: Given the minimally invasive, nondestructive nature of percutaneous PNS and the significant benefits experienced by participants who were recalcitrant to nonsurgical treatments, percutaneous PNS may provide a promising first-line neurostimulation treatment option for patients with chronic axial back pain.

A Systematic Literature Review of Peripheral Nerve Stimulation Therapies for the Treatment of Pain.

OBJECTIVE: To conduct a systematic literature review of peripheral nerve stimulation (PNS) for pain. DESIGN: Grade the evidence for PNS. METHODS: An international interdisciplinary work group conducted a literature search for PNS. Abstracts were reviewed to select studies for grading. Inclusion/exclusion criteria included prospective randomized controlled trials (RCTs) with meaningful clinical outcomes that were not part of a larger or previously reported group. Excluded studies were retrospective, had less than two months of follow-up, or existed only as abstracts. Full studies were graded by two independent reviewers using the modified Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria. RESULTS: Peripheral nerve stimulation was studied in 14 RCTs for a variety of painful conditions (headache, shoulder, pelvic, back, extremity, and trunk pain). Moderate to strong evidence supported the use of PNS to treat pain. CONCLUSION: Peripheral nerve stimulation has moderate/strong evidence. Additional prospective trials could further refine appropriate populations and pain diagnoses.

A Comprehensive Practice Guideline for Magnetic Resonance Imaging Compatibility in Implanted Neuromodulation Devices.

OBJECTIVES: The evolution of neuromodulation devices in order to enter magnetic resonance imaging (MRI) scanners has been one of understanding limitations, engineering modifications, and the development of a consensus within the community in which the FDA could safely administer labeling for the devices. In the initial decades of neuromodulation, it has been contraindicated for MRI use with implanted devices. In this review, we take a comprehensive approach to address all the major products currently on the market in order to provide physicians with the ability to determine when an MRI can be performed for each type of device implant. MATERIALS AND METHODS: We have prepared a narrative review of MRI guidelines for currently marketed implanted neuromodulation devices including spinal cord stimulators, intrathecal drug delivery systems, peripheral nerve stimulators, deep brain stimulators, vagal nerve stimulators, and sacral nerve stimulators. Data sources included relevant literature identified through searches of PubMed, MEDLINE/OVID, SCOPUS, and manual searches of the bibliographies of known primary and review articles, as well as manufacturer-provided information. RESULTS: Guidelines and recommendations for each device and their respective guidelines for use in and around MR environments are presented. CONCLUSIONS: This is the first comprehensive guideline with regards to various devices in the market and MRI compatibility from the American Society of Pain and Neuroscience.

Therapy Habituation at 12 Months: Spinal Cord Stimulation Versus Dorsal Root Ganglion Stimulation for Complex Regional Pain Syndrome Type I and II.

The ACCURATE randomized, controlled trial compared outcomes of dorsal root ganglion (DRG) stimulation versus tonic spinal cord stimulation (SCS) in 152 subjects with chronic lower extremity pain due to complex regional pain syndrome (CRPS) type I or II. This ACCURATE substudy was designed to evaluate whether therapy habituation occurs with DRG stimulation as compared to SCS through 12-months. A modified intention-to-treat analysis was performed to assess percentage pain relief (PPR) and responder rates at follow-up visits (end-of-trial, 1, 3, 6, 9, 12-months postpermanent implant) for all subjects that completed trial stimulation (DRG:N = 73, SCS:N = 72). For both groups, mean PPR was significantly greater at end-of-trial (DRG = 82.2%, SCS =0 77.0%) than all other follow-ups. Following permanent DRG system implantation, none of the time points were significantly different from one another in PPR (range = 69.3-73.9%). For the SCS group, PPR at 9-months (58.3%) and 12-months (57.9%) was significantly less than at 1-month (66.9%). The responder rate also decreased for the SCS group from 1-month (68.1%) to 12-months (61.1%). After stratifying by diagnosis, it was found that only the CRPS-I population had diminishing pain relief with SCS. DRG stimulation resulted in more stable pain relief through 12-months, while tonic SCS demonstrated therapy habituation at 9- and 12-months. Trial Registration: The ACCURATE study was registered at ClinicalTrials.gov with Identifier NCT01923285. PERSPECTIVE: This article reports on an ACCURATE substudy, which found that long-term therapy habituation occurred at 12-months with SCS, but not DRG stimulation, in patients with CRPS. The underlying mechanisms of action for these results remain unclear, although several lines of inquiry are proposed.

10 kHz SCS therapy for chronic pain, effects on opioid usage: Post hoc analysis of data from two prospective studies.

Chronic pain, including chronic low back and leg pain are prominent causes of disability worldwide. While patient management aims to reduce pain and improve daily function, prescription of opioids remains widespread despite significant adverse effects. This study pooled data from two large prospective trials on 10 kHz spinal cord stimulation (10 kHz SCS) in subjects with chronic low back pain and/or leg pain and performed post hoc analysis on changes in opioid dosage 12 months post 10 kHz SCS treatment. Patient-reported back and leg pain using the visual analog scale (VAS) and opioid dose (milligrams morphine equivalent/day, MME/day) were compared at 12 months post-10 kHz SCS therapy to baseline. Results showed that in the combined dataset, 39.3% of subjects were taking >90 MME dose of opioids at baseline compared to 23.0% at 12 months post-10 kHz SCS therapy (p = 0.007). The average dose of opioids in >90 MME group was significantly reduced by 46% following 10 kHz SCS therapy (p < 0.001), which was paralleled by significant pain relief (P < 0.001). In conclusion, current analysis demonstrates the benefits of 10 kHz SCS therapy and offers an evidence-based, non-pharmaceutical alternative to opioid therapy and/or an adjunctive therapy to facilitate opioid dose reduction whilst delivering significant pain relief. Healthcare providers involved in management of chronic non-cancer pain can include reduction or elimination of opioid use as part of treatment plan when contemplating 10 kHz SCS.

Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months: a randomized comparative trial.

Animal and human studies indicate that electrical stimulation of dorsal root ganglion (DRG) neurons may modulate neuropathic pain signals. ACCURATE, a pivotal, prospective, multicenter, randomized comparative effectiveness trial, was conducted in 152 subjects diagnosed with complex regional pain syndrome or causalgia in the lower extremities. Subjects received neurostimulation of the DRG or dorsal column (spinal cord stimulation, SCS). The primary end point was a composite of safety and efficacy at 3 months, and subjects were assessed through 12 months for long-term outcomes and adverse events. The predefined primary composite end point of treatment success was met for subjects with a permanent implant who reported 50% or greater decrease in visual analog scale score from preimplant baseline and who did not report any stimulation-related neurological deficits. No subjects reported stimulation-related neurological deficits. The percentage of subjects receiving ≥50% pain relief and treatment success was greater in the DRG arm (81.2%) than in the SCS arm (55.7%, P < 0.001) at 3 months. Device-related and serious adverse events were not different between the 2 groups. Dorsal root ganglion stimulation also demonstrated greater improvements in quality of life and psychological disposition. Finally, subjects using DRG stimulation reported less postural variation in paresthesia (P < 0.001) and reduced extraneous stimulation in nonpainful areas (P = 0.014), indicating DRG stimulation provided more targeted therapy to painful parts of the lower extremities. As the largest prospective, randomized comparative effectiveness trial to date, the results show that DRG stimulation provided a higher rate of treatment success with less postural variation in paresthesia intensity compared to SCS.

Novel 10-kHz High-frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: The SENZA-RCT Randomized Controlled Trial.

BACKGROUND: Current treatments for chronic pain have limited effectiveness and commonly known side effects. Given the prevalence and burden of intractable pain, additional therapeutic approaches are desired. Spinal cord stimulation (SCS) delivered at 10 kHz (as in HF10 therapy) may provide pain relief without the paresthesias typical of traditional low-frequency SCS. The objective of this randomized, parallel-arm, noninferiority study was to compare long-term safety and efficacy of SCS therapies in patients with back and leg pain. METHODS: A total of 198 subjects with both back and leg pain were randomized in a 1:1 ratio to a treatment group across 10 comprehensive pain treatment centers. Of these, 171 passed a temporary trial and were implanted with an SCS system. Responders (the primary outcome) were defined as having 50% or greater back pain reduction with no stimulation-related neurological deficit. RESULTS: At 3 months, 84.5% of implanted HF10 therapy subjects were responders for back pain and 83.1% for leg pain, and 43.8% of traditional SCS subjects were responders for back pain and 55.5% for leg pain (P < 0.001 for both back and leg pain comparisons). The relative ratio for responders was 1.9 (95% CI, 1.4 to 2.5) for back pain and 1.5 (95% CI, 1.2 to 1.9) for leg pain. The superiority of HF10 therapy over traditional SCS for leg and back pain was sustained through 12 months (P < 0.001). HF10 therapy subjects did not experience paresthesias. CONCLUSION: HF10 therapy promises to substantially impact the management of back and leg pain with broad applicability to patients, physicians, and payers.

Use of a newly developed delivery device for percutaneous introduction of multiple lead configurations for spinal cord stimulation.

OBJECTIVE: The Epiducer lead delivery system is a novel lead delivery device that can be used to percutaneously implant S-Series paddle leads (St. Jude Medical, Plano, TX, USA) as well as multiple percutaneous leads obviating the need for laminectomy and/or multiple needle sticks, respectively. This study evaluates the safety and usage of the Epiducer lead delivery system. METHODS: An Institutional Review Board-approved observational data collection study was conducted to evaluate usage patterns of the Epiducer system. In addition to the number and frequency of different lead configurations, the following procedural aspects of the surgery were recorded during the evaluation: angle of entry, distance from entry to final lead placement, and physician feedback. Descriptive statistics on adverse events, procedural aspects, and patient outcomes were compiled. RESULTS: Data were collected from 163 patients across 25 investigational sites. Physicians successfully implanted patients using the Epiducer during 89% of the procedures. Seven possible lead configurations were implanted. There were 96% and 92% of physicians "satisfied" or "very satisfied" with accessing the epidural space and placing multiple leads with the Epiducer delivery system, respectfully. Eighty-nine percent of physicians were "satisfied" or "very satisfied" with implanting an S-Series paddle lead using the Epiducer delivery system. Ninety-five percent of physicians were "satisfied" or "very satisfied" with the Epiducer delivery system overall. Ten patients (6%) experienced adverse events. CONCLUSION: Results suggest that the Epiducer delivery system allows for the safe and successful percutaneous implantation of paddle leads and/or multiple lead configurations. Furthermore, physicians are satisfied with the Epiducer delivery system.

The prospective evaluation of safety and success of a new method of introducing percutaneous paddle leads and complex arrays with an epidural access system.

OBJECTIVES: Spinal cord stimulation (SCS) has become a mainstay in the continuum of care for patients suffering from chronic neuropathic pain of the trunk and limbs. Options for placing these devices have included a percutaneous method of using an epidural needle to place a cylindrical (percutaneous) lead to stimulate the spinal cord, or an open laminotomy method for placing a paddle lead at the location of the surgical decompression of the laminae. Both of these methods have been successful in a high percentage of patients, but neither have been ideal. Limitations of the percutaneous leads have been inefficiency of power delivery, inability to achieve desired depth of stimulation in the spinal cord, occasional lead migration and difficulty covering complex pain patterns. Limitations of the paddle lead have been the need for surgical laminotomy, inability to steer the lead once placed, limits on placement in the vicinity of the surgical decompression, and a perceived risk of increased bleeding and trauma to the tissue. These factors have led many minimally invasive spine specialists to seek new options for SCS. This paper presents the initial US experience with a newly approved device to place both paddle leads, and multi-lead arrays into the epidural space via a percutaneous Seldinger-guided approach through a single needle placement. We will both describe the technique and review the outcomes of some of the early cases. MATERIALS AND METHODS: After Investigational Review Board clearance, patients consented to data collection in a prospective fashion regarding the use of a new percutaneous epidural introducer (Epiducer, St. Jude Neurological, Minneapolis, MN, USA) to place paddle leads and complex lead arrays. The patients underwent education regarding expectations and risks of the procedure consistent with our normal preoperative period. Patients underwent preoperative anesthesia screening and proper testing as outlined by the Joint Commission on Hospital Accreditation, and were given the opportunity to ask questions concerning the procedure. Once the patient wished to move forward, they were consented using the approved case reporting form and followed during the course of their care. The initial cases were performed in West Virginia with subsequent cases following at the other centers involved in this analysis. The outcomes of this analysis focused on three areas: 1. The technical success in placing the percutaneous sheath. This included the ability to successfully complete: • epidural access with a 14-gauge Tuohy needle • ability to place a styleted guidewire • ability to introduce the introduction system over the wire into the epidural space • ability to remove the guidewire and introduction tip leaving the 10-gauge sheath intact. 2. The ability to place the desired lead or leads into the epidural space via the percutaneous introduction sheath. 3. The presence of any major adverse event which were defined as: • nerve injury • paraplegia • worsening of baseline pain • epidural hematoma • epidural infection • dural tear • dural rent • retained device that could not be removed. This information was carefully recorded for each implant, and summarized in this communication. RESULTS: During the initial 30 days of the evaluation period, 43 epidural introduction systems were attempted in 38 patients. In patients in whom more than one paddle lead was placed, the system required the reinsertion of the guidewire through the Epiducer, removal of the Epiducer, and rewiring over the guidewire. This is necessary because the diameter of a paddle lead does not allow two or three leads to be placed without rewiring the system. The success of placement was 42/43, with inability to access the epidural space in one patient in whom ligamentum flavum hypertrophy was present on the preoperative imaging study. In all patients, the system was placed at the L1-L2 level, or lower, based on the Food and Drug Administration labeling. The total numbers of leads placed were 75, with both paddle and percutaneous arrays implanted successfully. There were no adverse events during this prospective surveillance evaluation. Ten patients complained of soreness at the entry site and post-procedure stiffness. These complaints were treated with ice, rest, and analgesics and resolved without incident. CONCLUSION: This paper describes the initial US cases of the placement of a paddle lead via a minimally invasive percutaneous method, as well as complex cylindrical arrays with a single needle entry to the epidural space. The device functioned successfully and presented a safe option for placing paddle leads and complex arrays.