High-frequency (10 kHz) spinal cord stimulation (SCS) as a salvage therapy for failed traditional SCS: A narrative review of the available evidence.

INTRODUCTION: Traditional spinal cord stimulation (t-SCS) has been used to treat chronic pain for over 50 years. However, up to 30% of patients undergo explant, with the main indication being loss of efficacy (LoE), and few alternative treatment options exist for these patients. Strategies to mitigate LoE commonly include conversion to another type of SCS (termed 'salvage' or 'rescue'). This review summarizes the existing literature concerning the efficacy and safety of 10 kHz SCS as a salvage therapy. METHODS: We searched PubMed, the Cochrane Library, ClinicalTrials.gov, and other sources between January 2009 and April 2021. Records were retained if the authors reported clinical outcomes with a minimum of ≥ 3 months of follow-up in patients implanted with a Senza® 10 kHz SCS system in an effort to treat t-SCS LoE. RESULTS: Ten articles were eligible for inclusion, reporting 3 prospective studies and 7 retrospective reviews. In the single study that salvaged patients without a repeat trial prior to surgery, 81% of patients were responders (≥ 50% pain relief from baseline), with mean pain relief of 60%. Among repeat-trial studies, the responder rate ranged from 46% to 80%, and mean pain relief from 47% to 68%. No unanticipated therapy-related safety issues were reported among the included articles. CONCLUSION: Preliminary data suggest that chronic back and/or leg pain patients with t-SCS LoE can experience improved and durable pain relief after conversion to 10 kHz SCS. However, additional research is needed to define predictors of success and establish whether salvage without a repeat trial is a viable conversion method.

A prospective, randomised, double-blind, placebo-controlled study to examine the effectiveness of burst spinal cord stimulation patterns for the treatment of failed back surgery syndrome.

OBJECTIVES: Spinal cord stimulation (SCS) for the treatment of chronic pain is a well-established therapy. However, the requirement that paresthesia be continually felt by the patient has important downsides. This study evaluated the effectiveness of a new paresthesia-free SCS paradigm, called burst stimulation, for the treatment of failed back surgery syndrome (FBSS) with a prospective, randomized, double-blind, placebo-controlled design. MATERIALS AND METHODS: Twenty patients with FBSS and a preexisting SCS system each received three treatment allocations in random order for a period of one week: 500-Hz tonic stimulation, burst stimulation, and placebo stimulation. The primary outcome measure was pain intensity measured on a numerical rating scale (NRS). Secondary outcome measures were pain quality measured using the Short-Form McGill Pain Questionnaire (SFMPQ) and safety. Additional data were collected relating to pain-related disability measured using the Oswestry Disability Index (ODI). RESULTS: The lowest mean NRS and SFMPQ scores were observed under burst stimulation. For the burst stimulation treatment group, mean NRS and SFMPQ scores were significantly decreased compared with the other treatment groups. Mean NRS and SFMPQ scores were not significantly different between 500-Hz tonic stimulation and placebo stimulation. Although the lowest mean ODI score was observed under burst stimulation, no significant differences were found between the ODI categories. No adverse events occurred, and burst stimulation was significantly preferred by 16 patients (80%). CONCLUSIONS: Overall, burst stimulation resulted in significantly better pain relief and improved pain quality in the short term compared with 500-Hz tonic stimulation and placebo stimulation and was preferred by the majority of patients.

Painful Peripheral Neuropathies of the Lower Limbs and/or Lower Extremities Treated with Spinal Cord Stimulation: A Systematic Review with Narrative Synthesis.

Introduction: Painful peripheral neuropathy (PPN) is a debilitating condition with varied etiologies. Spinal cord stimulation (SCS) is increasingly used when conservative treatments fail to provide adequate pain relief. Few published reviews have examined SCS outcomes in all forms of PPN. Methods: We conducted a systematic review of SCS in PPN. The PubMed database was searched up to February 7th, 2022, for peer-reviewed studies of SCS that enrolled PPN patients with pain symptoms in their lower limbs and/or lower extremities. We assessed the quality of randomized controlled trial (RCT) evidence using the Cochrane risk of bias tool. Data were tabulated and presented narratively. Results: Twenty eligible studies documented SCS treatment in PPN patients, including 10 kHz SCS, traditional low-frequency SCS (t-SCS), dorsal root ganglion stimulation (DRGS), and burst SCS. In total, 451 patients received a permanent implant (10 kHz SCS, n=267; t-SCS, n=147; DRGS, n=25; burst SCS, n=12). Approximately 88% of implanted patients had painful diabetic neuropathy (PDN). Overall, we found clinically meaningful pain relief (≥30%) with all SCS modalities. Among the studies, RCTs supported the use of 10 kHz SCS and t-SCS to treat PDN, with 10 kHz SCS providing a higher reduction in pain (76%) than t-SCS (38-55%). Pain relief with 10 kHz SCS and DRGS in other PPN etiologies ranged from 42-81%. In addition, 66-71% of PDN patients and 38% of nondiabetic PPN patients experienced neurological improvement with 10 kHz SCS. Conclusion: Our review found clinically meaningful pain relief in PPN patients after SCS treatment. RCT evidence supported the use of 10 kHz SCS and t-SCS in the diabetic neuropathy subpopulation, with more robust pain relief evident with 10 kHz SCS. Outcomes in other PPN etiologies were also promising for 10 kHz SCS. In addition, a majority of PDN patients experienced neurological improvement with 10 kHz SCS, as did a notable subset of nondiabetic PPN patients.

Long-term efficacy of high-frequency (10 kHz) spinal cord stimulation for the treatment of painful diabetic neuropathy: 24-Month results of a randomized controlled trial.

AIMS: To evaluate the long-term efficacy of high-frequency (10 kHz) spinal cord stimulation (SCS) for treating refractory painful diabetic neuropathy (PDN). METHODS: The SENZA-PDN study was a prospective, multicenter, randomized controlled trial that compared conventional medical management (CMM) alone with 10 kHz SCS plus CMM (10 kHz SCS+CMM) in 216 patients with refractory PDN. After 6 months, participants with insufficient pain relief could cross over to the other treatment. In total, 142 patients with a 10 kHz SCS system were followed for 24 months, including 84 initial 10 kHz SCS+CMM recipients and 58 crossovers from CMM alone. Assessments included pain intensity, health-related quality of life (HRQoL), sleep, and neurological function. Investigators assessed neurological function via sensory, reflex, and motor tests. They identified a clinically meaningful improvement relative to the baseline assessment if there was a significant persistent improvement in neurological function that impacted the participant's well-being and was attributable to a neurological finding. RESULTS: At 24 months, 10 kHz SCS reduced pain by a mean of 79.9% compared to baseline, with 90.1% of participants experiencing ≥50% pain relief. Participants had significantly improved HRQoL and sleep, and 65.7% demonstrated clinically meaningful neurological improvement. Five (3.2%) SCS systems were explanted due to infection. CONCLUSIONS: Over 24 months, 10 kHz SCS provided durable pain relief and significant improvements in HRQoL and sleep. Furthermore, the majority of participants demonstrated neurological improvement. These long-term data support 10 kHz SCS as a safe and highly effective therapy for PDN. TRIAL REGISTRATION: ClincalTrials.gov Identifier, NCT03228420.

Indirect Comparison of 10 kHz Spinal Cord Stimulation (SCS) versus Traditional Low-Frequency SCS for the Treatment of Painful Diabetic Neuropathy: A Systematic Review of Randomized Controlled Trials.

Spinal cord stimulation (SCS) is increasingly used to treat painful diabetic neuropathy (PDN). At the time of a recent meta-analysis in this field, data were only available from randomized controlled trials (RCTs) of traditional low-frequency SCS (LF-SCS). However, outcomes from high-frequency 10 kHz SCS treatment are now available. Our study aimed to systematically review the contemporary evidence for SCS in patients with lower limb pain due to PDN and include an indirect comparison of the high- and low-frequency modalities. We searched the PubMed/CENTRAL databases up to 18 August 2022, for peer-reviewed RCTs of SCS that enrolled PDN patients with lower limb pain symptoms. The quality of the evidence was assessed with the Cochrane Risk of Bias tool. Using SCS treatment arm data from the RCTs, we indirectly compared the absolute treatment effect of 10 kHz SCS and LF-SCS. Results are presented in tables and forest plots. This systematic review was reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. Three RCTs met our eligibility criteria, including the recent 10 kHz SCS RCT (N = 216, 90 implanted) and 2 others that examined LF-SCS (N = 36, 17 implanted; N = 60, 37 implanted). Our analysis of 6-month data found clinically meaningful pain relief with each SCS modality. However, significantly greater pain reduction was identified for 10 kHz SCS over LF-SCS: average pain reduction in the 10 kHz SCS cohort was 73.7% compared with 47.5% in the pooled LF-SCS group (p < 0.0001). In the permanent implant subset, the 50% pain reduction responder rate was 83.3% in the 10 kHz SCS cohort versus 63.0% in the pooled LF-SCS group (p = 0.0072). The overall risk of bias of each included RCT was deemed high, mainly due to the absence of patient blinding. Our analysis indicates that paresthesia-free 10 kHz SCS can provide superior pain relief and responder rate over LF-SCS for managing PDN patients refractory to conventional medical management.

Concept of the Number Needed to Treat for the Analysis of Pain Relief Outcomes in Patients Treated with Spinal Cord Stimulation.

In the rapidly evolving field of spinal cord stimulation (SCS), measures of treatment effects are needed to help understand the benefits of new therapies. The present article elaborates the number needed to treat (NNT) concept and applies it to the SCS field. We reviewed the basic theory of the NNT, its calculation method, and its application to historical controlled trials of SCS. We searched the literature for controlled studies with ≥20 implanted SCS patients with chronic axial back and/or leg pain followed for ≥3 months and a reported responder rate defined as ≥50% pain relief. Relevant data necessary to estimate the NNT were extracted from the included articles. In total, 12 of 1616 records were eligible for inclusion. The records reported 10 clinical studies, including 7 randomized controlled trials, 2 randomized crossover trials, and 1 controlled cohort study. The studies investigated traditional SCS and more recently developed SCS modalities, including 10 kHz SCS. In conclusion, the NNT estimate may help SCS stakeholders better understand the effect size difference between compared treatments; however, interpretation of any NNT should take into account its full context. In addition, comparisons across trials of different therapies should be avoided since they are prone to interpretation biases.

Efficacy and Safety of 10 kHz Spinal Cord Stimulation for the Treatment of Chronic Pain: A Systematic Review and Narrative Synthesis of Real-World Retrospective Studies.

10 kHz spinal cord stimulation (SCS) is increasingly utilized globally to treat chronic pain syndromes. Real-world evidence complementing randomized controlled trials supporting its use, has accumulated over the last decade. This systematic review aims to summarize the retrospective literature with reference to the efficacy and safety of 10 kHz SCS. We performed a systematic literature search of PubMed between 1 January 2009 and 21 August 2020 for English-language retrospective studies of ≥3 human subjects implanted with a Senza® 10 kHz SCS system and followed-up for ≥3 months. Two independent reviewers screened titles/abstracts of 327 studies and 46 full-text manuscripts. In total, 16 articles were eligible for inclusion; 15 reported effectiveness outcomes and 11 presented safety outcomes. Follow-up duration ranged from 6-34 months. Mean pain relief was >50% in most studies, regardless of follow-up duration. Responder rates ranged from 67-100% at ≤12 months follow-up, and from 46-76% thereafter. 32-71% of patients decreased opioid or nonopioid analgesia intake. Complication incidence rates were consistent with other published SCS literature. Findings suggest 10 kHz SCS provides safe and durable pain relief in pragmatic populations of chronic pain patients. Furthermore, it may decrease opioid requirements, highlighting the key role 10 kHz SCS can play in the medium-term management of chronic pain.

10 kHz spinal cord stimulation for the treatment of chronic back and/or leg pain: Summary of clinical studies.

Chronic pain has a major impact on sufferers and their families. The associated health care costs are substantial. In the context of increasing prevalence, effective treatment options are ever more important. 10 kHz spinal cord stimulation has been shown to effectively provide pain relief, aid in opioid reduction, and improve quality of life in patients with chronic intractable pain. The present review aims to summarize the clinical evidence related to the use of 10 kHz SCS in chronic back and/or leg pain. We searched the PubMed database between 2009 and 2 June 2020 for articles reporting clinical studies that included at least 10 human subjects permanently treated with a 10 kHz SCS system (Senza® system) for chronic back and/or leg pain for a minimum of 3 months. A randomized controlled trial (SENZA-RCT), as well as several prospective and retrospective studies, reported clinical outcomes in subjects with chronic back and leg pain treated with 10 kHz SCS. A high proportion of subjects (60%-80%) reported long-term response to therapy. Pain relief was provided without paresthesia. Other studies showed promising pain relief outcomes in subjects with back pain ineligible for spinal surgery, neuropathic limb pain, and in those with previously failed traditional low-frequency SCS. Most studies reported improved quality of life metrics and/or reduced opioid intake. Level 1 evidence has already been established for the use of 10 kHz SCS in treating chronic back and leg pain, corroborated by real-world, clinical experience. Exploratory studies also show the potential of the therapy in other refractory pain syndromes, although larger studies are desired to validate their findings. Overall, the literature suggests that 10 kHz SCS provides long-term pain relief in a high proportion of patients, along with improved quality of life and reduced opioid consumption.

A multicenter real-world review of 10 kHz SCS outcomes for treatment of chronic trunk and/or limb pain.

Objectives: High-frequency spinal cord stimulation (HF-SCS) at 10 kHz has proven to be efficacious in the treatment of chronic back and leg pain in a randomized, controlled, trial (SENZA-RCT). However, large observational studies have yet to be published. Therefore, we performed a real-world, multicenter, retrospective, review of therapy efficacy in 1660 patients with chronic trunk and/or limb pain. Methods: Data were collected in a real-world environment and retrospectively sourced from a global database. Included patients were trialed and/or permanently implanted with HF-SCS at 10 kHz between April 2014 and January 2018. We evaluated responder rates at 3, 6, and 12 months post-implantation. Response was defined as ≥50% pain relief from baseline. A last visit analysis included responder rate along with overall change in function, sleep, quality of life, and medication intake versus baseline. Results: Eighty-four percent of our HF-SCS-treated patients had both chronic back and leg pain. At least 70% of patients reported response to therapy throughout 12 months of follow-up. This sustained responder rate was corroborated by the last visit value (74.1%). Most patients reported concomitant improvements in function (72.3%), sleep (68.0%), and quality of life (90.3%) at their last visit versus baseline. Thirty-two percent of patients reported decreased medication intake at their last visit. Interpretation: Sustained and effective pain relief was experienced by >70% of our HF-SCS-treated patients, consistent with the findings of a previously published randomized, controlled, trial. Our review provides complementary evidence to support the treatment of chronic back and leg pain with this therapy.

Can transventricular intracardiac impedance measurement discriminate haemodynamically unstable ventricular arrhythmias in human?

AIMS: To measure changes in transventricular impedance during arrhythmias. METHODS AND RESULTS: Patients were studied during electrophysiological studies. A quadrapolar catheter was positioned at the right ventricular apex (RVA) and a decapolar catheter within the coronary sinus (CS). Transventricular impedance was measured by injecting a subthreshold biphasic rectangular pulse of 600 micro A between poles 1 of the CS catheter and pole 1 of the RVA catheter and the voltage measured between CS pole 10 and RVA catheter pole 4. Stroke impedance (SZ), surface ECG, intracardiac electrogram (IEGM), and invasive femoral artery blood pressure (FAP) were recorded. Twenty-eight patients were analysed, 5 with inducible, haemodynamically unstable ventricular tachycardia (VT) (HUSVT), 5 with stable VT (HSVT). During HUSVT, the SZ value reduced to 22% (range 0.15-0.32 P < 0.001) in comparison with sinus rhythm. For HSVT, the SZ value reduced to 58% (range 0.33-0.88) P < 0.01, significantly different from HUSVT (P < 0.01). There was a good correlation between reduction of SZ and arterial pulse pressure (PP) during arrhythmias (r = 0.95). CONCLUSION: Changes in SZ strongly correlated with PP amplitude. Transventricular impedance fell significantly during unstable arrhythmias and may be useful as a sensor capable of haemodynamic discrimination.

The use of unipolar intracardiac impedance for discrimination of haemodynamically stable and unstable arrhythmias in man.

AIMS: To determine the feasibility of discriminating haemodynamically stable from unstable arrhythmias using right ventricular (RV) unipolar intracardiac impedance (Z). METHODS AND RESULTS: A quadrapolar temporary pacing electrode was positioned at the RV apex and unipolar impedance was measured between the tip electrode and a surface patch electrode. Changes in peak-to-peak Z amplitude were measured simultaneously with surface ECG and blood pressure during induced arrhythmias. Haemodynamic instability was defined as a systolic pressure of <90 mmHg. There were 25 episodes of ventricular fibrillation (VF) induced in 15 patients, 18 episodes of ventricular tachycardia in 16 patients, and 33 episodes of supraventricular tachycardia (SVT) in 16 patients. Compared with the baseline rhythm, mean Z amplitude reduced from 51.3+/-7.7 to 11.2+/-7.4 Ohm (P<0.001) during VF, from 52.2+/-6.3 to 21.7+/-10.1 Ohm (P<0.01) during haemodynamically unstable VT, from 55.0+/-6.9 to 39.9+/-11 Ohm (ns) during stable VT, and from 56.4+/-8.4 to 36.9+/-9.3 Ohm during SVT (P<0.001). CONCLUSION: Right ventricular unipolar impedance is an adequate sensor for determining mechanical ventricular contraction and acts as a surrogate marker for a fall in arterial blood pressure during VF. However, for ventricular and supraventricular tachycardias, variations between patients did not allow adequate discrimination between stable and unstable arrhythmias.