Traditional Spinal Cord Stimulation Research Articles

ID: 216095 High-Frequency Spinal Cord Stimulation (SCS) in Patients Converted From Traditional SCS: A Case Series

Spinal cord stimulation (SCS) is an evidence-based intervention for treating chronic neuropathic pain1. However, with traditional SCS, around 30% of patients may require explant for reasons including loss of efficacy during treatment2. High-frequency SCS (10kHz SCS) has been reported to demonstrate long-term superiority compared to traditional low-frequency (LF) SCS3. Furthermore, converting from LF to 10kHz SCS can restore pain relief in patients experiencing loss of efficacy4. In this study, we present a case series of 6 patients converted from LF SCS to 10kHz therapy due to loss of efficacy.

ID: 197327 Clinical Outcomes Using A New Fast-Acting Sub-Perception Therapy For Chronic Pain: A European Observational Study

Traditional Spinal Cord Stimulation (SCS) modalities that achieve sub-perception analgesia (e.g., ∼ 1-10 kHz, BurstDR) require patients to often wait hours or even days until pain relief is fully realized. A recent study however has demonstrated that quicker analgesic onset is possible using a new sub-threshold-based SCS modality called Fast-Acting Sub-Perception Therapy (FAST).1 While achieving rapid onset of pain relief offers a substantial advantage for patients and providers alike, the magnitude and quality of pain relief in patients using FAST in the real-world clinical setting is also an important consideration. As such, we sought to assess outcomes in patients using FAST-SCS for chronic pain in a European-based, multicenter, observational study.

ID: 203617 One-Year Safety Analysis Using DRG-Stimulation for the Treatment of Lower Limbs CRPS I and II

Dorsal root ganglion stimulation (DRG-S) is effective for the treatment of chronic focal pain conditions1 and superior to traditional spinal cord stimulation (SCS) in the treatment of CRPS types I and II (causalgia).2,3 To provide continued evidence of safety after FDA approval, a post-market, prospective, single-arm, observational study in patients with CRPS types I or II of the lower limbs treated with DRG-S was designed (NCT02800863). The primary goal of the study was to show that the proportion of serious adverse effects (SAEs) in subjects who received a permanent implant was lower than a pre-specified goal of 15.5% after 12 months. SAEs were defined as safety-related device and non-device events that result in the subject's death or a serious deterioration in health that is life-threatening, results in permanent impairment, or requires medical intervention and hospitalization. The study descriptive endpoint was the proportion of subjects with device, procedure, or stimulation-related SAEs (SADE) or AE (ADE)

ID: 208527 Long-Term Clinical Outcomes of a Low-Energy Derivative Study of Differential Target Multiplexed Spinal Cord Stimulation

Differential Target MultiplexedTM spinal cord stimulation (SCS) is an established therapy that has shown superior back pain relief to traditional SCS.1 Derivatives of the DTMTM waveform are being investigated to understand opportunities for therapy personalization. Energy-conserving approaches altering amplitude, frequency, and pulse width, have the potential to impact patient experience with rechargeable and non-rechargeable devices.

ID: 212058 Modeling the Impact of a DTM(TM) Derivative on Rechargeable and Recharge-Free SCS Systems

Differential Target MultiplexedTM spinal cord stimulation (SCS) is an established therapy that has shown superior back pain relief to traditional SCS.1,2 Derivatives of the DTMTM SCS waveform are being investigated to understand opportunities to further tailor therapy approaches for different patients. A recent feasibility study demonstrated a DTMTM SCS derivative provided significant reduction in energy usage while offering a similar degree of pain relief and therapy satisfaction to patients compared to prior SCS therapy. Data collected to date from an ongoing RCT of the same reduced-energy DTMTM SCS derivative has been used to estimate device longevity for recharge-free devices as well as recharge requirements on rechargeable devices.

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

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. 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. 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. 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.

Differential target multiplexed spinal cord stimulator: a review of preclinical/clinical data and hardware advancement.

Spinal cord stimulation (SCS) is an effective neuromodulation technique for treating chronic neuropathic pain. Recent rapid growth in understanding its mechanism has led to the development of glial cell-based differential target multiplexed (DTM) stimulation and its derivative algorithm. Both preclinical research and clinical trials in humans showed superior pain relief using DTM SCS compared with traditional SCS. Another multicenter prospective clinical trial showed significant pain score reduction and energy saving using the DTM derivative algorithm. This review paper summarizes the evidence related to using DTM stimulation for other painful conditions such as nonsurgical low back pain and upper-limb pain. All these advanced programming options can be delivered using an innovative platform, the Medtronic Intellis™ neurostimulator.

Regulation of Expression of Extracellular Matrix Proteins by Differential Target Multiplexed Spinal Cord Stimulation (SCS) and Traditional Low-Rate SCS in a Rat Nerve Injury Model.

There is limited research on the association between the extracellular matrix (ECM) and chronic neuropathic pain. The objective of this study was twofold. Firstly, we aimed to assess changes in expression levels and the phosphorylation of ECM-related proteins due to the spared nerve injury (SNI) model of neuropathic pain. Secondly, two modalities of spinal cord stimulation (SCS) were compared for their ability to reverse the changes induced by the pain model back toward normal, non-injury levels. We identified 186 proteins as ECM-related and as having significant changes in protein expression among at least one of the four experimental groups. Of the two SCS treatments, the differential target multiplexed programming (DTMP) approach reversed expression levels of 83% of proteins affected by the pain model back to levels seen in uninjured animals, whereas a low-rate (LR-SCS) approach reversed 67%. There were 93 ECM-related proteins identified in the phosphoproteomic dataset, having a combined 883 phosphorylated isoforms. DTMP back-regulated 76% of phosphoproteins affected by the pain model back toward levels found in uninjured animals, whereas LR-SCS back-regulated 58%. This study expands our knowledge of ECM-related proteins responding to a neuropathic pain model as well as providing a better perspective on the mechanism of action of SCS therapy.

The Effectiveness of Various Types of Electrical Stimulation of the Spinal Cord for Chronic Pain in Patients with Postherpetic Neuralgia: A Literature Review.

Postherpetic neuralgia (PHN) is a severe condition that remains a challenge to treat. Spinal cord stimulation (SCS) is used in cases of insufficient efficacy of conservative treatment. However, in contrast to many other neuropathic pain syndromes, there is a huge problem in reaching long-term stable pain relief in patients with PHN using conventional tonic SCS. The objective of this article was to present a review of the current management strategies of PHN, their efficacy, and safety. We searched for articles containing the keywords "spinal cord stimulation AND postherpetic neuralgia," "high-frequency stimulation AND postherpetic neuralgia," "burst stimulation AND postherpetic neuralgia" and "dorsal root ganglion stimulation AND postherpetic neuralgia" in Pubmed, Web of Science, and Scopus databases. The search was limited to human studies published in the English language. There were no publication period limitations. Bibliographies and references of selected publications on neurostimulation for PHN were further manually screened. The full text of each article was studied once the abstract was analyzed by the searching reviewer and found appropriate. The initial search yielded 115 articles. Initial screening based on abstract and title allowed us to exclude 29 articles (letters, editorials, and conference abstracts). The full-text analysis allowed us to exclude another 74 articles (fundamental research articles, research utilizing animal subjects, and systemic and nonsystemic reviews) and results of PHN treatment presented with other conditions, leaving 12 articles for the final bibliography. 12 articles reporting on the treatment of 134 patients with PHN were analyzed, with a disproportionally large amount of traditional SCS treatment than that to alternative SCS: DRGS (13 patients), burst SCS (1 patient), and high-frequency SCS (2 patients). Long-term pain relief was achieved in 91 patients (67.9%). The mean VAS score improvement was 61.4% with a mean follow-up time of 12.85 months. Although the number of patients in alternative SCS studies was very limited, almost all of them showed good responses to therapy with more than 50% VAS improvement and reduction of analgesic dosage. The article contains a review analysis of 12 articles concerning the current methods of treatment for postherpetic neuralgia including conservative treatment, spinal cord stimulation, and novel neuromodulation strategies. Available information on the pathophysiology of PHN and the effect or stimulation on its course, together with a number of technical nuances concerning various types of neurostimulation are also elucidated in this article. A number of alternative invasive treatments of PHN are also discussed. Spinal cord stimulation is an established treatment option for patients with pharmacologically resistant PHN. High-frequency stimulation, burst stimulation, and dorsal root ganglion stimulation are promising options in the management of PHN due to the absence of paresthesias which can be painful for patients with PHN. But more research is still required to recommend the widespread use of these new methods.

Utilizing 10kHz Stimulation to Salvage a Failed Low Frequency Spinal Cord Stimulation Trial.

Spinal cord stimulation (SCS) is a viable treatment option for chronic pain. One of the primary indications for SCS implantation is persistent pain after spinal surgery. Studies have demonstrated that these patients have a better response to SCS over conservative management or repeat surgery. Traditional SCS therapy uses parasthesias to overlap a patient's pain pattern and provide relief, though some patients find this uncomfortable. To avoid the use of paresthesias, a 10kHz waveform can be utilized to provide a subthreshold level of high frequency stimulation to provide superior pain relief without paresthesias. Additionally, 10kHz stimulation may be used to salvage therapy when other forms of SCS have failed. Here, we present a case in which a patient was switched from traditional SCS to 10kHz in the middle of a SCS trial with lead placement revision to salvage SCS therapy.

A Novel Pulsed Stimulation Pattern in Spinal Cord Stimulation: Clinical Results and Postulated Mechanisms of Action in the Treatment of Chronic Low Back and Leg Pain

ObjectivesThe aim of this article is to discuss the possible mechanisms of action (MOAs) and results of a pilot study of a novel, anatomically placed, and paresthesia-independent, neurostimulation waveform for the management of chronic intractable pain. Materials and MethodsA novel, multilayered pulsed stimulation pattern (PSP) that comprises three temporal layers, a Pulse Pattern layer, Train layer, and Dosage layer, was developed for the treatment of chronic intractable pain. During preliminary development, the utility was evaluated of anatomical PSP (aPSP) in human subjects with chronic intractable pain of the leg(s) and/or low back, compared with that of traditional spinal cord stimulation (T-SCS) and physiological PSP. The scientific theory and testing presented in this article provide the preliminary justification for the potential MOAs by which PSP may operate. ResultsDuring the pilot study, aPSP (n = 31) yielded a greater decrease in both back and leg pain than did T-SCS (back: −60% vs −46%; legs: −63% vs −43%). In addition, aPSP yielded higher responder rates for both back and leg pain than did T-SCS (61% vs 48% and 78% vs 50%, respectively). DiscussionThe novel, multilayered approach of PSP may provide multimechanistic therapeutic relief through preferential fiber activation in the dorsal column, optimization of the neural onset response, and use of both the medial and lateral pathway through the thalamic nuclei. The results of the pilot study presented here suggest a robust responder rate, with several subjects (five subjects with back pain and three subjects with leg pain) achieving complete relief from PSP during the acute follow-up period. These clinical findings suggest PSP may provide a multimechanistic, anatomical, and clinically effective management for intractable chronic pain. Because of the limited sample size of clinical data, further testing and long-term clinical assessments are warranted to confirm these preliminary findings.

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

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 10kHz SCS as a salvage therapy. 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 ≥ 3months of follow-up in patients implanted with a Senza® 10kHz SCS system in an effort to treat t-SCSLoE. 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. 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 10kHz SCS. However, additional research is needed to define predictors of success and establish whether salvage without a repeat trial is a viable conversion method.

Spinal Cord Stimulation for Painful Diabetic Neuropathy.

Spinal cord stimulation (SCS) technology has been recently approved by the US Food and Drug Administration (FDA) for painful diabetic neuropathy (PDN). The treatment involves surgical implantation of electrodes and a power source that delivers electrical current to the spinal cord. This treatment decreases the perception of pain in many chronic pain conditions, such as PDN. The number of patients with PDN treated with SCS and the amount of data describing their outcomes is expected to increase given four factors: (1) the large number of patients with this diagnosis, (2) the poor results that have been obtained for pain relief with pharmacotherapy and noninvasive non-pharmacotherapy, (3) the results to date with investigational SCS technology, and (4) the recent FDA approval of systems that deliver this treatment. Whereas traditional SCS replaces pain with paresthesias, a new form of SCS, called high-frequency 10-kHz SCS, first used for pain in 2015, can relieve PDN pain without causing paresthesias, although not all patients experience pain relief by SCS. This article describes (1) an overview of SCS technology, (2) the use of SCS for diseases other than diabetes, (3) the use of SCS for PDN, (4) a comparison of high-frequency 10-kHz and traditional SCS for PDN, (5) other SCS technology for PDN, (6) deployment of SCS systems, (7) barriers to the use of SCS for PDN, (8) risks of SCS technology, (9) current recommendations for using SCS for PDN, and (10) future developments in SCS.

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.

PO126 / #702 CLINICAL OUTCOMES USING A NEW FAST-ACTING SUB-PERCEPTION THERAPY FOR CHRONIC PAIN: A MULTICENTER EUROPEAN OBSERVATIONAL REAL-WORLD STUDY: E-POSTER VIEWING

Traditional Spinal Cord Stimulation (SCS) modalities that achieve sub-perception analgesia (e.g., ∼1-10 kHz, burst SCS) require patients to often wait hours or even days until pain relief is fully realized. A recent study however has demonstrated that quicker analgesic onset is possible using a new sub-threshold-based SCS modality called Fast-Acting Sub-Perception Therapy (FAST).1 While achieving rapid onset of pain relief offers a substantial advantage for patients and providers alike, the magnitude and quality of pain relief in patients using FAST in the real-world clinical setting is also an important consideration.

O125 / #658 EFFECT OF LOW-FREQUENCY DORSAL ROOT GANGLION STIMULATION IN THE TREATMENT OF NEUROPATHIC AND NOCICEPTIVE PAIN: TRACK 4: SCS

Dorsal root ganglion stimulation has become a key tool in neuromodulation for chronic pain in the past years. Stimulation designs for DRG-S are not as well understood and as sophisticated as in traditional spinal cord stimulation. It is assumed, that specific neural components can be preferably influenced at specific frequencies. We have investigated mid to high frequencies recently. In this study we double-blinded, prospectively investigated treatment response to patterns including low stimulation frequencies.

PO191 / #725 SUCCESSFUL REDUCTION OF CHRONIC UPPER LIMB AND NECK PAIN USING DIFFERENTIAL TARGET MULTIPLEXED SCS: E-POSTER VIEWING

Treatment of intractable neuropathic pain using traditional spinal cord stimulation with cervically-placed leads has been challenging due to the possible occurrence of uncomfortable paresthesia caused by neck motion. While there are multiple SCS studies demonstrating successful treatment of lower extremity pain (e.g., back and leg pain), studies demonstrating successful treatment of upper extremity pain are sparse. We conducted a prospective, multi-center study to evaluate the safety and efficacy of Differential Target Multiplexed SCS in subjects diagnosed with chronic upper extremity pain.

PO142 / #674 EFFECTIVENESS OF UPPER THORACIC AND CERVICAL DORSAL ROOT GANGLION STIMULATION FOR CHRONIC INTRACTABLE PAIN MANAGEMENT: E-POSTER VIEWING

Dorsal root ganglia stimulation (DRG-S) has established its role as a superior treatment to traditional spinal cord stimulation for lower extremity CRPS I and II (site ACCURATE). While primarily used in the low thoracic and sacral regions, recent literature has shown that DRG-S can be safe and effective in the upper thoracic and cervical regions.1 As incidences of upper extremities CRPS are more frequent than lower extremities,2 there is a need for expansion of treatment options for this debilitating pain condition.

O126 / #684 EUROPEAN RANDOMIZED CONTROLLED TRIAL TO STUDY THE EFFECTS OF DIFFERENTIAL TARGET MULTIPLEXED SCS IN TREATING INTRACTABLE CHRONIC BACK PAIN WITHOUT PREVIOUS LUMBAR SPINE SURGERY: TRACK 3: NEUROSTIMULATION FOR BACK AND LEG PAIN

Differential target multiplexed spinal cord stimulation (SCS) utilizes various signals that are multiplexed spatially and temporally. A recent report of a randomized controlled trial (RCT) showed that differential target multiplexed SCS provided superior long-term back pain responder rate (subjects with ≥50% pain relief) relative to traditional SCS in subjects mostly diagnosed with persistent spinal pain syndrome. The study demonstrated the sustainability of the benefit of differential target multiplexed SCS therapy on back and leg pain[1].

PO158 / #871 MODELING THE IMPACT OF A DIFFERENTIAL TARGET MULTIPLEXED DERIVATIVE ON RECHARGEABLE AND RECHARGE-FREE SPINAL CORD STIMULATION SYSTEMS USING RESULTS FROM THE ENDURANCE STUDY: E-POSTER VIEWING

Differential target multiplexed Spinal Cord Stimulation (SCS) is an established therapy that has shown superior back pain relief to traditional SCS.1,2 Derivatives of the differential target multiplexed SCS waveform are being investigated to understand opportunities to further tailor therapy approaches for different patients. A recent feasibility study demonstrated a differential target multiplexed SCS derivative provided significant reduction in energy usage while offering a similar degree of pain relief and therapy satisfaction to patients compared to prior SCS therapy.