European randomized controlled trial evaluating differential target multiplexed spinal cord stimulation and conventional medical management in subjects with persistent back pain ineligible for spine surgery: 24-month results.

BACKGROUND: Differential target multiplexed spinal cord stimulation (DTM SCS) was shown to be superior to conventional SCS for treating chronic low back pain (CLBP) in subjects with persistent spinal pain syndrome with previous spinal surgery (PSPS-T2) or ineligible for it (PSPS-T1). This study reports 24-month efficacy and safety of DTM SCS vs. conventional medical management (CMM) in PSPS-T1 subjects across four European countries. METHODS: This is a prospective, multicenter, open-label, randomized, controlled trial with optional crossover. Subjects randomized 1:1 to DTM SCS or CMM. Primary endpoint was responder rate (% subjects reporting ≥50% CLBP relief) at 6 months. A superiority test compared responder rates between treatments. CLBP and leg pain levels, functional disability, quality of life (QoL), patient satisfaction and global impression of change were evaluated for 24 months. A Composite Responder Index (CRI) was obtained using CLBP relief, disability and QoL. Incidence of study-related adverse events evaluated safety. RESULTS: A total of 55 and 57 subjects were randomized to DTM SCS and CMM respectively. DTM SCS was superior, with CLBP responder rates ≥80% and CLBP relief >5.6 cm (>70% reduction) through the 24-month follow-up. Improvements with DTM SCS in other outcomes were sustained. The CRI was >80% for DTM SCS through 24 months. Opioid medication intake decreased in subjects treated with DTM SCS. Most patients treated with DTM SCS felt satisfied and improved at the end of the study. Safety was congruent with other studies. CONCLUSION: DTM SCS is efficacious and safe during 24 months for the treatment of CLBP and leg pain in PSPS-T1 patients ineligible for spine surgery. SIGNIFICANCE STATEMENT: This randomized controlled trial shows that Differential Target Multiplexed SCS (DTM SCS) is an effective and safe long-term treatment for PSPS type 1 patients suffering from axial low back pain with or without leg pain and who are ineligible for spinal surgery. Currently, CMM treatments are their only option and provide limited benefits. Besides superior pain relief, DTM SCS provides significant improvements in functional disability, quality of life, high levels of satisfaction and perceived impression of change.

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

OBJECTIVES: 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. METHODS: 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). RESULTS: 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. DISCUSSION: Current evidence shows that closed-loop and fixed-output SCS provide more benefits and are cost-saving compared to CMM for patients with NSRBP.

Large-scale real-world data on a multidisciplinary approach to spinal cord stimulation for persistent spinal pain syndromes: first evaluation of the Neuro-Pain® nationwide screening and follow-up interactive register.

Introduction: Spinal cord stimulation is a common treatment option for neuropathic pain conditions. Despite its extensive use and multiple technological evolutions, long term efficacy of spinal cord stimulation is debated. Most studies on spinal cord stimulation include a rather limited number of patients and/or follow-ups over a limited period. Therefore, there is an urgent need for real-world, long-term data. Methods: In 2018, the Belgian government initiated a nationwide secure platform for the follow-up of all new and existing spinal cord stimulation therapies. This is a unique approach used worldwide. Four years after the start of centralized recording, the first global extraction of data was performed. Results: Herein, we present the findings, detailing the different steps in the centralized procedure, as well as the observed patient and treatment characteristics. Furthermore, we identified dropouts during the screening process, the reasons behind discontinuation, and the evolution of key indicators during the trial period. In addition, we obtained the first insights into the evolution of the clinical impact of permanent implants on the overall functioning and quality of life of patients in the long-term. Discussion: Although these findings are the results of the first data extraction, some interesting conclusions can be drawn. The long-term outcomes of neuromodulation are complex and subject to many variables. Future data extraction will allow us to identify these confounding factors and the early predictors of success. In addition, we will propose further optimization of the current process.

Examining the Duration of Carryover Effect in Patients With Chronic Pain Treated With Spinal Cord Stimulation (EChO Study): An Open, Interventional, Investigator-Initiated, International Multicenter Study.

OBJECTIVES: Spinal cord stimulation (SCS) is a surgical treatment for severe, chronic, neuropathic pain. It is based on one to two lead(s) implanted in the epidural space, stimulating the dorsal column. It has long been assumed that when deactivating SCS, there is a variable interval before the patient perceives the return of the pain, a phenomenon often termed echo or carryover effect. Although the carryover effect has been problematized as a source of error in crossover studies, no experimental investigation of the effect has been published. This open, prospective, international multicenter study aimed to systematically document, quantify, and investigate the carryover effect in SCS. MATERIALS AND METHODS: Eligible patients with a beneficial effect from their SCS treatment were instructed to deactivate their SCS device in a home setting and to reactivate it when their pain returned. The primary outcome was duration of carryover time defined as the time interval from deactivation to reactivation. Central clinical parameters (age, sex, indication for SCS, SCS treatment details, pain score) were registered and correlated with carryover time using nonparametric tests (Mann-Whitney/Kruskal-Wallis) for categorical data and linear regression for continuous data. RESULTS: In total, 158 patients were included in the analyses. A median carryover time of five hours was found (interquartile range 2.5;21 hours). Back pain as primary indication for SCS, high-frequency stimulation, and higher pain score at the time of deactivation were correlated with longer carryover time. CONCLUSIONS: This study confirms the existence of the carryover effect and indicates a remarkably high degree of interindividual variation. The results suggest that the magnitude of carryover may be correlated to the nature of the pain condition and possibly stimulation paradigms. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03386058.

Heart rate variability is not suitable as a surrogate marker for pain intensity in patients with chronic pain.

ABSTRACT: The search towards more objective outcome measurements and consequently surrogate markers for pain started decades ago; however, no generally accepted biomarker for pain has qualified yet. The goal is to explore the value of heart rate variability (HRV) as surrogate marker for pain intensity chronic pain setting. Pain intensity scores and HRV were collected in 366 patients with chronic pain, through a cross-sectional multicenter study. Pain intensity was measured with both the visual analogue scale and numeric rating scale, whereas 16 statistical HRV parameters were derived. Canonical correlation analysis was performed to evaluate the correlation between the dependent pain variables and the HRV parameters. Surrogacy was determined for each HRV parameter with point estimates between 0 and 1 whereby values close to 1 indicate a strong association between the surrogate and the true endpoint at the patient level. Weak correlations were revealed between HRV parameters and pain intensity scores. The highest surrogacy point estimate was found for mean heart rate as marker for average pain intensity on the numeric rating scale with point estimates of 0.0961 (95% confidence interval [CI] 0.0384-0.1537) and 0.0209 (95% CI 0-0.05) for patients without medication use and with medication, respectively. This study indicated that HRV parameters as separate entities are no suitable surrogacy candidates for pain intensity, in a population of chronic pain patients. Further potential surrogate candidates and clinical robust true endpoints should be explored, to find a surrogate measure for the highly individual pain experience.

Applicability and Validity of an e-Health Tool for the Appropriate Referral and Selection of Patients With Chronic Pain for Spinal Cord Stimulation: Results From a European Retrospective Study.

OBJECTIVES: To support rational decision-making on spinal cord stimulation (SCS), a European expert panel developed an educational e-health tool using the RAND/University of California at Los Angeles Appropriateness Method. This retrospective study aimed to determine the applicability and validity of the tool using data from patients for whom SCS had been considered. MATERIALS AND METHODS: A total of 12 European implant centers retrieved data from 25 to 50 consecutive patients for whom SCS was considered in 2018-2019. For each patient, data were captured on the clinical and psychosocial variables included in the e-health tool, center decisions on SCS, and patient outcomes. Patient outcomes included global perception of effect by the patient and observer, and pain reduction (numeric pain rating scale) at six-month follow-up. RESULTS: In total, 483 patients were included, of whom 133 received a direct implant, 258 received an implant after a positive trial, 32 had a negative trial, and 60 did not receive SCS for reasons other than a negative trial. The most frequent indication was persistent spinal pain syndrome type 1 and type 2 (74%), followed by neuropathic pain syndromes (13%), complex regional pain syndrome (12%), and ischemic pain syndromes (0.8%). Data on the clinical and psychosocial variables were complete for 95% and 93% of patients, respectively, and missing data did not have a significant impact on the study outcomes. In patients who had received SCS, panel recommendations were significantly associated with patient outcomes (p < 0.001 for all measures). Substantial improvement ranged from 25% if the e-health tool outcome was "not recommended" to 83% if SCS was "strongly recommended". In patients who underwent a trial (N = 290), there was 3% of trial failure when SCS was "strongly recommended" vs 46% when SCS was "not recommended". CONCLUSIONS: Retrospective application of the e-health tool on patient data showed a strong relationship between the panel recommendations and both SCS trial results and treatment outcomes.

Patient selection for spinal cord stimulation: The importance of an integrated assessment of clinical and psychosocial factors.

BACKGROUND: A previously developed educational e-health tool considers both clinical and psychosocial factors when selecting patients with chronic pain for spinal cord stimulation (SCS). The validity of the composite recommendations was evaluated in a retrospective study, demonstrating a strong relationship with patient outcomes after SCS. METHODS: An additional retrospective analysis was performed to determine the added value of a psychosocial evaluation as part of the decision-making process on SCS. Data concerned 482 patients who were considered for SCS in 2018-2019. The analysis focused on the relationship between the different layers of the tool recommendations (clinical, psychosocial, composite) with trial results and patient outcomes at 6 months after SCS. Of the initial study population, 381 patients underwent SCS and had follow-up data on at least one of three pain-related outcome measures. RESULTS: Pain improvement was observed in 76% of the patients for whom SCS was strongly recommended based on merely the clinical aspects. This percentage varied by the level of psychosocial problems and ranged from 86% in patients without any compromising psychosocial factors to 60% in those with severe problems. Similarly, the severity of psychosocial problems affected trial results in patients for whom SCS was either recommended or strongly recommended. CONCLUSIONS: The strong relationship between psychosocial factors embedded in the SCS e-health tool and patient outcomes supports an integrated and multidisciplinary approach in the selection of patients for SCS. The educational e-health tool, combining both clinical and psychosocial aspects, is believed to be helpful for further education and implementation of this approach. SIGNIFICANCE STATEMENT: This study confirms the relevance of the psychosocial factors embedded in the educational SCS e-health tool (https://scstool.org/). The strong relationship between the severity of psychosocial factors with patient outcomes supports conducting a comprehensive psychological and behavioural assessment when determining the eligibility of patients for SCS.

High-frequency (10 kHz) spinal cord stimulation for the treatment of focal, chronic postsurgical neuropathic pain: results from a prospective study in Belgium.

Aim: Chronic postsurgical pain (CPSP) is a common complication of surgery. This study was conducted to evaluate the efficacy and safety of paresthesia-free, 10-kHz spinal cord stimulation (SCS) as a treatment for CPSP. Patients & methods: Subjects in this prospective, single-arm study had an average pain intensity of ≥5 cm on a 10-cm visual analog scale. The subjects who had pain relief of ≥50% (response) with temporary trial stimulation were permanently implanted with 10-kHz SCS and assessed for 1 year. Results: At 12 months, 94% of subjects were responders to 10-kHz SCS, and 88% had pain remission (visual analog scale ≤2.5 cm). Conclusion: The pain relief was durable in CPSP subjects and the safety profile of 10-kHz SCS was as expected. Clinical Trial registration number: VT005076953 (Privacy Commission of Belgium).

A paramedian approach for dorsal root ganglion stimulation placement developed to limit lead migration and fracture.

INTRODUCTION: Dorsal root ganglion stimulation (DRG-S), has demonstrated superiority in the treatment of complex regional pain syndrome and causalgia. Lead migration and fracture impact DRG-S therapeutic stability. Lead anchoring reduces DRG-S lead migration without increasing lead fracture. Lead fracture may be related to lead entrapment in the superficial fascial plane. A novel medialized approach for lead placement and anchoring is presented to address these issues. METHODS: We suggest an alternative technique for implanting percutaneous DRG-S leads at the T10-L5 levels. RESULTS: A novel medialized ipsilateral technique for lead placement and anchoring for single, bilateral, and adjacent segment placement is presented. The Tuohy needle puncture site is medial to the pedicle and adjacent to the spinous process, two vertebral levels caudad to the target foramen. Trajectory is maintained in the sagittal plane, to access the caudad interlaminar space near the midline. This technique allows for ipsilateral or contralateral lead placement. After epidural access, the introducer sheath is rotated toward the targeted foramen and advanced. The guidewire followed by the lead is passed, and once lead position is confirmed, tension "S" loops are created, followed by anchoring to the deep fascia. CONCLUSION: We describe a new paramedian technique for DRG-S lead placement. We propose it will decrease DRG-S complication rates through anchoring to reduce migration and by avoiding the fascial planes thought to be responsible for fracture. Long-term outcomes applying our proposed techniques are required for determining the true impact, however, early anecdotal results suggest that these new techniques are favorable.

Appropriate referral and selection of patients with chronic pain for spinal cord stimulation: European consensus recommendations and e-health tool.

BACKGROUND: Spinal cord stimulation (SCS) is an established treatment for chronic neuropathic, neuropathic-like and ischaemic pain. However, the heterogeneity of patients in daily clinical practice makes it often challenging to determine which patients are eligible for this treatment, resulting in undesirable practice variations. This study aimed to establish patient-specific recommendations for referral and selection of SCS in chronic pain. METHODS: A multidisciplinary European panel used the RAND/UCLA Appropriateness Method (RUAM) to assess the appropriateness of (referral for) SCS for 386 clinical scenarios in four pain areas: chronic low back pain and/or leg pain, complex regional pain syndrome, neuropathic pain syndromes and ischaemic pain syndromes. In addition, the panel identified a set of psychosocial factors that are relevant to the decision for SCS treatment. RESULTS: Appropriateness of SCS was strongly determined by the neuropathic or neuropathic-like pain component, location and spread of pain, anatomic abnormalities and previous response to therapies targeting pain processing (e.g. nerve block). Psychosocial factors considered relevant for SCS selection were as follows: lack of engagement, dysfunctional coping, unrealistic expectations, inadequate daily activity level, problematic social support, secondary gain, psychological distress and unwillingness to reduce high-dose opioids. An educational e-health tool was developed that combines clinical and psychosocial factors into an advice on referral/selection for SCS. CONCLUSIONS: The RUAM was useful to establish a consensus on patient-specific criteria for referral/selection for SCS in chronic pain. The e-health tool may help physicians learn to apply an integrated approach of clinical and psychosocial factors. SIGNIFICANCE: Determining the eligibility of SCS in patients with chronic pain requires careful consideration of a variety of clinical and psychosocial factors. Using a systematic approach to combine evidence from clinical studies and expert opinion, a multidisciplinary European expert panel developed detailed recommendations to support appropriate referral and selection for SCS in chronic pain. These recommendations are available as an educational e-health tool (https://www.scstool.org/).

A Novel Minimally Invasive Wireless Technology for Neuromodulation via Percutaneous Intercostal Nerve Stimulation for Post-Herpetic Neuralgia: A Case Report with Short-Term Follow-up.

BACKGROUND: Peripheral nerve stimulation of primary afferent neurons provides control of localized chronic pain. This technique applies permanent electrical stimulation at the target area via a minimally invasive, subcutaneous placement of an electrode. OBJECTIVE: To assess the analgesic effects of minimally invasive wireless neuromodulation in the treatment of chronic intractable pain secondary to post-herpetic neuralgia. CASE SUMMARY: A 78-year-old man presented with severe intractable post-herpetic neuralgic pain. He was known to have non-Hodgkin's lymphoma under remission following treatment with chemotherapy and stem cell transplantation, twice. He also developed steroid-induced diabetes mellitus during this treatment. In view of his compromised immune status, he was deemed a suitable candidate for our minimally invasive neuromodulation technology. Two subcutaneous electrodes were placed on the right-hand side of the trunk, 10 cm medial and parallel to the spinous process at the level of T7-T8 under fluoroscopic guidance along the T7 intercostal nerve. The external transmitter was worn with a belt over a single layer of clothing and used to transmit power to the stimulator. The entire procedure required only a small incision for the introduction of the electrode placement. RESULTS: After an uneventful procedure, the pain score decreased from 8 to 3, with a reduction in pain medication. The EuroQol Five Dimensions Questionnaire scores were 0.102 before the trial, 0.630 at 1 month, and 0.576 at 3 months. CONCLUSIONS: Subcutaneous placement of electrodes with our minimally invasive technique and wireless neuromodulation technology was safe and effective. Significant improvements in pain relief ensued, and no further adverse events had been reported at the end of 3 months' follow-up.

Wireless Neuromodulation for Chronic Back Pain: Delivery of High-Frequency Dorsal Root Ganglion Stimulation by a Minimally Invasive Technique.

OBJECTIVE: To evaluate the analgesic effect of a dorsal root ganglion (DRG) stimulation technology utilizing high-frequency pulse rates to treat intractable chronic back and leg pain. METHODS: This case study presents the outcomes, with a novel, wireless, minimally invasive miniature neurostimulator system in a case of chronic back pain. The subject was implanted bilaterally with a Freedom 4A quadripolar electrode array at the L2 dorsal root ganglion. Stimulation was applied using 10 kHz pulse rate and 30 µs pulse width. A VAS pain-rating scale, Oswestry Disability Index (ODI), EQ-5D-5L Quality of Life Questionnaire 5 dimensions, and Patients' Global Impression of Change (PGIC) scale were evaluated at 12 weeks and 6 months post implantation. RESULTS: VAS pain scores for back pain reduced from 91 to 31 mms and 80 to 35 mms for leg pain. Additionally, while stimulation remained paresthesia-free, there were a marked decrease in pain medications and an increase in quality of life. Also, an increase in functionality from crippled to moderate was reported. There were no adverse reactions related to the procedure or device. CONCLUSION: The minimally invasive, wireless approach to deliver high-frequency, paresthesia-free DRG stimulation for treatment of chronic back and leg pain associated with FBSS was effective and encouraging.