Durability of Evoked Compound Action Potential (ECAP)-Controlled, Closed-Loop Spinal Cord Stimulation (SCS) in a Real-World European Chronic Pain Population.

INTRODUCTION: Closed-loop spinal cord stimulation (CL-SCS) is a recently introduced system that records evoked compound action potentials (ECAPs) from the spinal cord elicited by each stimulation pulse and uses this information to automatically adjust the stimulation strength in real time, known as ECAP-controlled SCS. This innovative system compensates for fluctuations in the distance between the epidural leads and the spinal cord by maintaining the neural response (ECAP) at a predetermined target level. This data collection study was designed to assess the performance of the first CL-SCS system in a real-world setting under normal conditions of use in multiple European centers. The study analyzes and presents clinical outcomes and electrophysiological and device data and compares these findings with those reported in earlier pre-market studies of the same system. METHODS: This prospective, multicenter, observational study was conducted in 13 European centers and aimed to gather electrophysiological and device data. The study focused on the real-world application of this system in treating chronic pain affecting the trunk and/or limbs, adhering to standard conditions of use. In addition to collecting and analyzing basic demographic information, the study presents data from the inaugural patient cohort permanently implanted at multiple European centers. RESULTS: A significant decrease in pain intensity was observed for overall back or leg pain scores (verbal numerical rating score [VNRS]) between baseline (mean ± standard error of the mean [SEM]; n = 135; 8.2 ± 0.1), 3 months (n = 93; 2.3 ± 0.2), 6 months (n = 82; 2.5 ± 0.3), and 12 months (n = 76; 2.5 ± 0.3). Comparison of overall pain relief (%) to the AVALON and EVOKE studies showed no significant differences at 3 and 12 months between the real-world data release (RWE; 71.3%; 69.6%) and the AVALON (71.2%; 73.6%) and EVOKE (78.1%; 76.7%) studies. Further investigation was undertaken to objectively characterize the physiological parameters of SCS therapy in this cohort using the metrics of percent time above ECAP threshold (%), dose ratio, and dose accuracy (µV), according to previously described methods. Results showed that a median of 90% (40.7-99.2) of stimuli were above the ECAP threshold, with a dose ratio of 1.3 (1.1-1.4) and dose accuracy of 4.4 µV (0.0-7.1), based on data from 236, 230, and 254 patients, respectively. Thus, across all three metrics, the majority of patients had objective therapy metrics corresponding to the highest levels of pain relief in previously reported studies (usage over threshold > 80%, dose ratio > 1.2, and error < 10 µV). CONCLUSIONS: In conclusion, this study provides valuable insights into the real-world application of the ECAP-controlled CL-SCS system, highlighting its potential for maintaining effective pain relief and objective neurophysiological therapy metrics at levels seen in randomized control trials, and potential for quantifying patient burden associated with SCS system use via patient-device interaction metrics. CLINICAL TRIAL REGISTRATION: In the Netherlands, the study is duly registered on the International Clinical Trials Registry Platform (Trial NL7889). In Germany, the study is duly registered as NCT05272137 and in the United Kingdom as ISCRTN27710516 and has been reviewed by the ethics committee in both countries.

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

INTRODUCTION: 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. METHODS: 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 3 months, 6 months, and 12 months 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. RESULTS: 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)], 3 months (n = 12; 1.9 ± 0.5), 6 months (n = 16; 2.6 ± 0.5), and 12 months (n = 20; 2.0 ± 0.5), with 85.0% of the patients being satisfied at 12 months. Additionally, no significant differences in average pain relief at 3 months and 12 months 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. CONCLUSIONS: 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 12 months and corroborate the outcomes observed in the AVALON prospective, multicenter, single-arm study and the EVOKE double-blind, multicenter, randomized controlled trial. TRIAL REGISTRATION: The data collection is registered on the International Clinical Trials Registry Platform (Trial NL7889).

Comparing the Efficacy of Dorsal Root Ganglion Stimulation With Conventional Medical Management in Patients With Chronic Postsurgical Inguinal Pain: Post Hoc Analyzed Results of the SMASHING Study.

OBJECTIVES: Approximately 10% of patients who undergo inguinal hernia repair or Pfannenstiel incision develop chronic (> three months) postsurgical inguinal pain (PSIP). If medication or peripheral nerve blocks fail, a neurectomy is the treatment of choice. However, some patients do not respond to this treatment. In such cases, stimulation of the dorsal root ganglion (DRG) appears to significantly reduce chronic PSIP in selected patients. MATERIALS AND METHODS: In this multicenter, randomized controlled study, DRG stimulation was compared with conventional medical management (CMM) (noninvasive treatments, such as medication, transcutaneous electric neurostimulation, and rehabilitation therapy) in patients with PSIP that was resistant to a neurectomy. Patients were recruited at a tertiary referral center for groin pain (SolviMáx, Eindhoven, The Netherlands) between March 2015 and November 2016. Suitability for implantation was assessed according to the Dutch Neuromodulation Association guidelines. The sponsor discontinued the study early owing to slow enrollment. Of 78 planned patients, 18 were randomized (DRG and CMM groups each had nine patients). Six patients with CMM (67%) crossed over to DRG stimulation at the six-month mark. RESULTS: Fifteen of the 18 patients met the six-month primary end point with a complete data set for a per-protocol analysis. Three patients with DRG stimulation had a negative trial and were lost to follow-up. The average pain reduction was 50% in the DRG stimulation and crossover group (from 6.60 ± 1.24 to 3.28 ± 2.30, p = 0.0029). Conversely, a 13% increase in pain was observed in patients with CMM (from 6.13 ± 2.24 to 6.89 ± 1.24, p = 0.42). Nine patients with DRG stimulation experienced a total of 19 adverse events, such as lead dislocation and pain at the implantation site. CONCLUSIONS: DRG stimulation is a promising effective therapy for pain relief in patients with PSIP resistant to conventional treatment modalities; larger studies should confirm this. The frequency of side effects should be a concern in a new study. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02349659.

Dutch Consensus Paper: A Consensus View on the Place of Neurostimulation Within the Treatment Arsenal of Five Reimbursed Indications for Neurostimulation in The Netherlands.

INTRODUCTION: After an interpretation trajectory, the Dutch Quality of Healthcare Institute recommended that for five indications, spinal cord stimulation, dorsal root ganglion stimulation, or occipital nerve stimulation, together referred to as neurostimulation, can be considered effective and be reimbursed in the Netherlands. These five indications are the well and largely studied, accepted neurostimulation indications in scientific literature. As an extension of this, all the scientific societies involved in the Netherlands were required to reach a consensus about the diagnosis and treatment of these five formulated indications to describe the place of neurostimulation within the treatment algorithm. This article describes the development process and content of the consensus paper. MATERIALS AND METHODS: A scientific committee, consisting of three anesthesiologists/pain physicians (one of whom acted as the working group's chair), a neurosurgeon, a neurologist, a rehabilitation physician, and three nurse practitioners, participated. A quality advisor of the Knowledge Institute of the Dutch Federation of Medical Specialists supported the committee. The committee participated on behalf of their various scientific and professional societies. Three sessions were organized during which the place of neurostimulation in the treatment algorithm of the five relevant indications was discussed extensively. A narrative literature review and experts' opinions formed the basis of decision-making in the process. RESULTS: For all five diagnoses, general and diagnosis-specific treatment requirements, conservative treatments, and minimally invasive treatments are listed. These treatments should be considered in the chronic pain management algorithm before eventually proceeding to neurostimulation. DISCUSSION/CONCLUSION: The content of this consensus view was discussed and compared with other literature on cost-effectiveness and the place in the algorithm of treating chronic pain. This Dutch consensus paper could ultimately contribute to the maintenance or expansion of neurostimulation and the reimbursement.

The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations for Surgical Technique for Spinal Cord Stimulation.

INTRODUCTION: The field of neurostimulation for the treatment of chronic pain is a rapidly developing area of medicine. Although neurostimulation therapies have advanced significantly as a result of technologic improvements, surgical planning, device placement, and postoperative care are of equal importance to optimize outcomes. This Neurostimulation Appropriateness Consensus Committee (NACC) project intends to provide evidence-based guidance for these often-overlooked areas of neurostimulation practice. MATERIALS AND METHODS: Authors were chosen based on 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 the last NACC publication in 2017 to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on evidence strength and consensus when evidence was scant. RESULTS: This NACC project provides guidance on preoperative assessment, intraoperative techniques, and postoperative management in the form of consensus points with supportive evidence. These results are based on grade of evidence, strength of consensus, and expert opinion. CONCLUSIONS: The NACC has given guidance for a surgical plan that encompasses the patient journey from the planning stage through the surgical experience and postoperative care. The overall recommendations are designed to improve efficacy and the safety of patients undergoing these neuromodulation procedures and are intended to apply throughout the international community.

Effectiveness and Safety of Dorsal Root Ganglion Stimulation for the Treatment of Chronic Pain: A Pooled Analysis.

INTRODUCTION: Since it became available in the mid-2010s, dorsal root ganglion (DRG) stimulation has become part of the armamentarium to treat chronic pain. To date, one randomized controlled trial, and several studies of moderate sample size and various etiologies have been published on this topic. We conducted a pooled analysis to investigate the generalizability of individual studies and to identify differences in outcome between chronic pain etiologic subgroups and/or pain location. MATERIALS AND METHODS: One prospective, randomized comparative trial and six prospective, single-arm, observational studies were identified that met pre-defined acceptance criteria. Pain scores and patient-reported outcome (PRO) measures were weighted by study sample sizes and pooled. Safety data are reported in aggregate form. RESULTS: Our analysis included 217 patients with a permanent implant at 12-month follow-up. Analysis of pooled data showed an overall weighted mean pain score of 3.4, with 63% of patients reporting ≥50% pain relief. Effectiveness sub-analyses in CRPS-I, causalgia, and back pain resulted in a mean reduction in pain intensity of 4.9, 4.6, and 3.9 points, respectively. Our pooled analysis showed a pain score for primary affected region ranging from 1.7 (groin) to 3.0 (buttocks) and responder rates of 80% for foot and groin, 75% for leg, and 70% for back. A substantial improvement in all PROs was observed at 12 months. The most commonly reported procedural or device complications were pain at the IPG pocket site, lead fracture, lead migration, and infection. CONCLUSIONS: DRG stimulation is an effective and safe therapy for various etiologies of chronic pain.

Prospective Cohort Analysis of DRG Stimulation for Failed Back Surgery Syndrome Pain Following Lumbar Discectomy.

INTRODUCTION: Surgical lumbar discectomy is a commonly performed routine spinal procedure that is usually undertaken to alleviate lumbar radicular symptoms caused by a herniated intervertebral disc. Surgical lumbar discectomy can also lead to chronic postsurgical leg and/or back pain (failed back surgery syndrome [FBSS]), a condition that can be refractory to conventional medical management. Early clinical results on the use of dorsal root ganglion (DRG) stimulation for FBSS have supported the use of this treatment alternative. METHODS: A multicenter, single-arm, observational cohort study enrolled patients who had chronic pain following surgical lumbar discectomy, had failed conservative treatments, and reported pain intensity of at least 6 out of 10 in the primary region of pain. Data were collected on pain, quality of life, disability, and mood at baseline and through 12 months. RESULTS: Thirteen patients underwent a trial of DRG stimulation; 11 (84.6%; 95% confidence interval = 57.8% to 95.7%) had good outcomes and underwent permanent device placement. Pain was reduced from a score of 8.64 (±0.92) at baseline to 2.40 (±2.38; n = 9) after 12 months of treatment, a 72.05% average reduction (P < 0.001). Similar improvements were observed across the secondary clinical measures, and safety data were in line with published rates. DISCUSSION: These results suggest that DRG stimulation induces pain relief in subjects diagnosed with FBSS. These reductions in pain were also associated with improvements in quality of life and disability. Additional prospective studies are warranted to further investigate this potential application of DRG stimulation, as well as to optimize patient selection, lead placement, and programming strategies.

The Neuromodulation Appropriateness Consensus Committee on Best Practices for Dorsal Root Ganglion Stimulation.

INTRODUCTION: The Neuromodulation Appropriateness Consensus Committee (NACC) is dedicated to improving the safety and efficacy of neuromodulation and thus improving the lives of patients undergoing neuromodulation therapies. With continued innovations in neuromodulation comes the need for evolving reviews of best practices. Dorsal root ganglion (DRG) stimulation has significantly improved the treatment of complex regional pain syndrome (CRPS), among other conditions. Through funding and organizational leadership by the International Neuromodulation Society (INS), the NACC reconvened to develop the best practices consensus document for the selection, implantation and use of DRG stimulation for the treatment of chronic pain syndromes. METHODS: The NACC performed a comprehensive literature search of articles about DRG published from 1995 through June, 2017. A total of 2538 article abstracts were then reviewed, and selected articles graded for strength of evidence based on scoring criteria established by the US Preventive Services Task Force. Graded evidence was considered along with clinical experience to create the best practices consensus and recommendations. RESULTS: The NACC achieved consensus based on peer-reviewed literature and experience to create consensus points to improve patient selection, guide surgical methods, improve post-operative care, and make recommendations for management of patients treated with DRG stimulation. CONCLUSION: The NACC recommendations are intended to improve patient care in the use of this evolving therapy for chronic pain. Clinicians who choose to follow these recommendations may improve outcomes.

Evaluating Dorsal Root Ganglion Stimulation in a Prospective Dutch Cohort.

OBJECTIVES: Dorsal root ganglion (DRG) stimulation is a recent neuromodulation option that has delivered safe, effective pain relief for a number of etiologies. This prospective observational study was intended to establish the effectiveness of this treatment in a typical real-world clinical context. MATERIALS AND METHODS: Participants with chronic, intractable pain of the trunk or lower limbs were recruited from multiple pain clinics in the Netherlands. Subjects were trialed and implanted with DRG stimulation systems. Pain, function, mood, and quality of life, ratings were collected through 12 months postimplant. RESULTS: Of the 66 subjects enrolled, failed back surgery syndrome, peripheral nerve injury, and complex regional pain syndrome formed the largest etiologies. Permanent implants were placed in 86.2% subjects (56/65). After 12 months of treatment, average pain ratings in subjects' primary area of pain decreased from 8.0 cm at baseline to 4.1 cm, and 49% of subjects had ≥50% reduction in pain (visual analog scale). In addition, functional capacity was increased, and mood and quality of life improved. No confirmed lead migrations were observed, and there was a low rate of infection. CONCLUSIONS: DRG stimulation significantly reduced the severity of subjects' pain and enabled participatory changes that improved quality of life through 12-months postimplant.

Spinal cord stimulation of the dorsal root ganglion for groin pain-a retrospective review.

BACKGROUND: Spinal cord stimulation (SCS) is a standard treatment option for chronic neuropathic pain. However, some anatomical pain distributions are known to be difficult to cover with traditional SCS-induced paresthesias and/or may also induce additional, unwanted stimulation. We present the results from a retrospective review of data from patients with groin pain of various etiologies treated using neuromodulation of the dorsal root ganglion (DRG). METHODS: Data from 29 patients with neuropathic groin pain were reviewed. Patients underwent trial therapy where specifically designed leads were implanted at the target DRGs between T12 and L4. Patients who had a successful trial (> 50% improvement) received the fully implantable neuromodulation system. Pain scores were captured on a visual analog scale (VAS) at baseline and at regular follow-up visits. RESULTS: Twenty-five patients (86.2%) received fully implantable neurostimulators, and the average follow-up period was 27.8 ± 4.3 (standard error of the mean, SEM) weeks. The average pain reduction was 71.4 ± 5.6%, and 82.6% (19/23) of patients experienced a > 50% reduction in their pain at the latest follow-up. Individual cases showed improvement with a variety of etiologies and pain distributions; a subanalysis of postherniorrhaphy cohort also showed significant improvement. CONCLUSIONS: Early findings suggest that neuromodulation of the DRG may be an effective treatment for chronic neuropathic pain conditions in the groin region. This technique offers a useful alternative for pain conditions that do not always respond optimally to traditional SCS therapy. Neuromodulation of the DRG provided excellent cross-dermatomal paresthesia coverage, even in cases with patients with discrete pain areas. The therapy can be specific, sustained, and independent of body position.

Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomized clinical trial.

Painful diabetic neuropathy (PDN) is a peripheral neuropathic pain condition that is often difficult to relieve. Spinal cord stimulation (SCS) is a proven effective therapy for various types of mixed neuropathic conditions, yet effectiveness of SCS treatment for PDN is not well established. To our knowledge, ours is the first multicentre randomized controlled trial investigating the effectiveness of SCS in patients with PDN. Sixty patients with PDN in the lower extremities refractory to conventional medical therapy were enrolled and followed for 6 months. They were randomized 2:1 to best conventional medical practice with (SCS group) or without (control group) additional SCS therapy, and both groups were assessed at regular intervals. At each follow-up visit, the EuroQoL 5D, the short form McGill Pain Questionnaire (SF-MPQ) and a visual analogue scale (VAS, ranging 0-100) to measure pain intensity were recorded. The average VAS score for pain intensity was 73 in the SCS group and 67 in the control group at baseline. After 6 months of treatment, the average VAS score was significantly reduced to 31 in the SCS group (P<.001) and remained 67 (P=.97) in the control group. The SF-MPQ and EuroQoL 5D questionnaires also showed that patients in the SCS group, unlike those in the control group, experienced reduced pain and improved health and quality of life after 6 months of treatment. In patients with refractory painful diabetic neuropathy, spinal cord stimulation therapy significantly reduced pain and improved quality of life.