A Retrospective Review of Real-world Outcomes Following 60-day Peripheral Nerve Stimulation for the Treatment of Chronic Pain.

BACKGROUND: Real-world data can provide important insights into treatment effectiveness in routine clinical practice. Studies have demonstrated that in multiple different pain indications temporary (60-day) percutaneous peripheral nerve stimulation (PNS) treatment can produce significant relief, but few real-world studies have been published. The present study is the first real-world, retrospective review of a large database depicting outcomes at the end of a 60-day PNS treatment period. OBJECTIVES: Evaluate outcomes during a 60-day PNS treatment in routine clinical practice. STUDY DESIGN: Secondary retrospective review. METHODS: Anonymized records of 6,160 patients who were implanted with a SPRINT PNS System from August 2019 through August 2022 were retrospectively reviewed from a national real-world database. The percentage of patients with ? 50% pain relief and/or improvement in quality of life was evaluated and stratified by nerve target. Additional outcomes included average and worst pain score, patient-reported percentage of pain relief, and patient global impression of change. RESULTS: Overall, 71% of patients (4,348/6,160) were responders with >= 50% pain relief and/or improvement in quality of life; pain relief among responders averaged 63%. The responder rate was largely consistent across nerve targets throughout the back and trunk, upper and lower extremities, and posterior head and neck. LIMITATIONS: This study was limited by its retrospective nature and reliance on a device manufacturer's database. Additionally, detailed demographic information and measures for pain medication usage and physical function were not assessed. CONCLUSIONS: This retrospective analysis supports recent prospective studies demonstrating that 60-day percutaneous PNS can provide significant relief across a wide range of nerve targets. These data serve an important role in complementing the findings of published prospective clinical trials.

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

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

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

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

Gasserian Ganglion Stimulation for Facial Pain.

Non-neuralgic trigeminal neuropathic pain can be challenging in terms of treatment as pharmacological interventions often tend to be ineffective. Within the pain-transmitting pathway, the Gasserian ganglion (GG) is a rather unique anatomical and physiological structure where the sensory (including pain) information from the entire half of the face undergoes primary processing in a very compact and clearly defined entity. Moreover, GG is positioned in a completely immobile intradural location (the Meckel's cave) and is insulated from the brain by a layer of dura. As a confluence of all three trigeminal branches, GG allows one to achieve clinical effect on the entire half of the face with a relatively small surgical intervention while maintaining an ability to select exact facial regions based on known somatotopic organization of nerve fibers. Therefore, when it comes to electrical neuromodulation, the GG stimulation (GGS) may be a unique solution for treatment of medically refractory facial pain. GGS was introduced in 1970s and continues to be a recognized surgical modality with multiple published clinical series describing multi-year experience in hundreds of facial pain patients. GGS is particularly useful in treatment of patients with chronic trigeminal neuropathic pain and persistent idiopathic facial pain who tried and failed or were not considered good candidates for the conventional surgical interventions. With advances in lead technology, intraoperative visualization and stereotactic navigation, percutaneous GGS became a minimally invasive surgical intervention that is recommended for consideration in complex facial pain. Here, we review the clinical data and summarize the current state of GGS in facial pain treatment.

Peripheral Nerve Stimulation for Facial Pain Using Wireless Devices.

Since its original introduction several decades ago, peripheral nerve stimulation (PNS) of the craniofacial region has been traditionally performed using devices intended for spinal cord stimulation applications with inevitably high rate of technical challenges and procedural complications. The lower invasiveness of recently developed wireless neurostimulation systems makes them much better suited for craniofacial applications. Here, we discuss the preliminary clinical data from several published reports and the ongoing multicenter prospective study of wireless PNS in the craniofacial region. Advances in wireless transmission of electrical signals may make wireless neurostimulation even more attractive in the future. Since most of the evidence supporting PNS for facial pain comes from small subsets of the population, case series and case reports, there will need to be larger, randomized controlled trials with cost efficacy analyses in order to validate the role of wireless PNS as the standard of care.

Peripheral Nerve Field Stimulation for Chronic Back Pain: Therapy Outcome Predictive Factors.

OBJECTIVE: To identify variables that influence pain reduction following peripheral nerve field stimulation (PNFS) in order to identify a potential responder profile. METHODS: Exploratory univariate and multivariate (random forest) analyses were performed separately on 2 randomized controlled trials and a registry; all included patients with chronic back pain, mainly failed back surgery syndrome. An international expert panel judged the clinical relevance of variables to identify responders by consensus. RESULTS: Variables identified that may help predict PNFS success in patients with back pain include patient and pain characteristics (age, time since onset of pain and spinal surgery, pain medication history, position and size of pain area, pain severity, mixed nociceptive/neuropathic pain, health-related quality of life, depression, functional disability, and leg pain status), implant procedure variables (the number and position of leads, paresthesia coverage, and amount of pain relief during the trial), and programming (number of programs, cathodes, and anodes; pulse rate; pulse width; and percentage of device usage). CONCLUSIONS: While these analyses are exploratory and restricted to a limited sample size, they suggest variables that may play a role in predicting a therapeutic response. These results, however, are informative only and should be cautiously interpreted. Future research to validate the variables in a clinical study is needed.

Occipital Nerve Stimulation.

Although the first publications on clinical use of peripheral nerve stimulation for the treatment of chronic pain came out in the mid-1960s, it took 10 years before this approach was used to stimulate the occipital nerves. The future for occipital nerve stimulation is likely to bring new indications, devices, stimulation paradigms, and a decrease in invasiveness. As experience increases, one may expect that occipital nerve stimulation will eventually gain regulatory approval for more indications, most likely for occipital neuralgia, migraines and cluster headaches. This process may require additional studies, at least for approval from the US Food and Drug Administration.

Concurrent Placement of Bilateral Suboccipital and Supraorbital Nerve Stimulators Using On-Q* Tunneler: Technical Note.

BACKGROUND: Stimulation of the occipital and supraorbital nerves is used to treat chronic migraine refractory to medical management. Placement of cranial leads is often challenging due to the rigid Touhy needle included in the kit for its placement. OBJECTIVE: To report the first case of concurrent placement of bilateral supraorbital (SNS) and occipital nerve stimulators (ONS) from a unilateral approach using the On-Q* Tunneler, (Halyard Health, Alpharetta, Georgia) a flexible, blunt tipped plastic tunneler with a tear-away sheath. METHODS: We present the case of a 49-yr-old female with debilitating daily holocephalic headaches who underwent placement of SNS and ONS through a cervical and left temporal incision at an outside hospital. She presented to our institution with purulent drainage from the temporal incision and the system was removed. We describe an alternative approach to bilateral SNS and ONS placement with a soft flexible tunneling device, which facilitated placement of the entire system through a right temporal incision, thereby avoiding her previously infected surgical sites. RESULTS: The patient reported complete resolution of her daily headaches and was able to resume her activities as a full-time student. CONCLUSION: The flexibility of the On-Q tunneler device (Halyard Health) allows the placement of bilateral SNS and ONS from a unilateral incision, thereby minimizing the cosmetic effect and infectious risk of this procedure.

Carotid Sinus/Nerve Stimulation for Treatment of Resistant Hypertension and Heart Failure.

Hypertension and cardiovascular disease are leading causes of morbidity and mortality worldwide. The prevalence of resistant hypertension remains high and is expected to increase. Moreover, there are limitations to therapeutic interventions aimed at treating resistant hypertension and heart failure despite the wide availability of therapeutic agents and dietary and lifestyle modification. Device-based therapy by baroreflex activation via carotid sinus/nerve stimulation is currently undergoing investigation, and promising findings from clinical trials have been published. Baroreflex activation therapy may represent a new approach for treatment of these conditions by reducing sympathetic drive and increasing parasympathetic activity. Here we describe a new technology which is designed to deliver carotid sinus stimulation to electrically activate the carotid baroreceptors and baroreflex, thereby reducing blood pressure and improving cardiac function. The theory, surgical techniques, and clinical trials of carotid sinus stimulation are highlighted.

Regulation of Peripheral Nerve Stimulation Technology.

The number of peripheral nerve stimulation (PNS) indications, targets, and devices is expanding, yet the development of the technology has been slow because many devices used for PNS do not have formal regulatory approval. Manufacturers have not sought Food and Drug Administration (FDA) approval for PNS devices because of a perceived lack of interest amongst practitioners and patients. Without FDA approval, companies cannot invest in marketing to educate the implanters and the patients about the benefits of PNS in the treatment of chronic pain. Violation of this has resulted in governmental investigation and prosecution. Most of the PNS devices currently used to treat chronic pain are FDA approved for epidural spinal cord stimulation. Many of the complications seen in PNS surgery can be attributed to the lack of purpose-built hardware with FDA approval. Despite the lack of regulatory approval, there are insurance companies that approve PNS procedures when deemed medically necessary. As the targets and indications for PNS continue to expand, there will be an even greater need for customized technological solutions. It is up to the medical device industry to invest in the design and marketing of PNS technology and seek out FDA approval. Market forces will continue to push PNS into the mainstream and physicians will increasingly have the choice to implant devices specifically designed and approved to treat chronic peripheral nerve pain.

Peripheral Nerve Stimulation for Pain in Extremities: An Update.

Pain in extremities may occur in a variety of central and peripheral neuropathic and nociceptive syndromes, some of which may respond to central neuromodulation procedures. Peripheral neuromodulation techniques, either as a stand-alone therapy or as an adjuvant to spinal cord stimulation, may be particularly effective when the pain is localized to a part of a single extremity or when the source of the pain is related to the malfunction of a known peripheral nerve. Further, peripheral neuromodulation is used to treat disorders in which central simulation fails to provide discrete therapeutic paresthesia. Despite the fact that there are only a few neuromodulatory devices designed specifically for the periphery, clinical experiences are growing, and here we provide a clinical update on use of peripheral nerve stimulation (PNS) in management of chronic pain in extremities. Historical PNS strategies and innovative methods are reviewed and highlighted in this chapter. With the upcoming technological advances and new stimulation paradigms, along with clear updated guidelines statements, the utilization of PNS will likely continue to increase and improve the management of chronic pain syndromes in the extremities. The potential success of the novel devices specifically designed to target the peripheral nervous system is expected to positively impact and promote the use of PNS in treatment of chronic pain.

Safety and efficacy of peripheral nerve stimulation of the occipital nerves for the management of chronic migraine: long-term results from a randomized, multicenter, double-blinded, controlled study.

BACKGROUND: Recent studies evaluated short-term efficacy and safety of peripheral nerve stimulation (PNS) of the occipital nerves for managing chronic migraine. We present 52-week safety and efficacy results from an open-label extension of a randomized, sham-controlled trial. METHODS: In this institutional review board-approved, randomized, multicenter, double-blinded study, patients were implanted with a neurostimulation system, randomized to an active or control group for 12 weeks, and received open-label treatment for an additional 40 weeks. Outcomes collected included number of headache days, pain intensity, migraine disability assessment (MIDAS), Zung Pain and Distress (PAD), direct patient reports of headache pain relief, quality of life, satisfaction and adverse events. Statistical tests assessed change from baseline to 52 weeks using paired t-tests. Intent-to-treat (ITT) analyses of all patients (N = 157) and analyses of only patients who met criteria for intractable chronic migraine (ICM; N = 125) were performed. RESULTS: Headache days were significantly reduced by 6.7 (±8.4) days in the ITT population (p < 0.001) and by 7.7 (±8.7) days in the ICM population (p < 0.001). The percentages of patients who achieved a 30% and 50% reduction in headache days and/or pain intensity were 59.5% and 47.8%, respectively. MIDAS and Zung PAD scores were significantly reduced for both populations. Excellent or good headache relief was reported by 65.4% of the ITT population and 67.9% of the ICM population. More than half the patients in both cohorts were satisfied with the headache relief provided by the device. A total of 183 device/procedure-related adverse events occurred during the study, of which 18 (8.6%) required hospitalization and 85 (40.7%) required surgical intervention; 70% of patients experienced an adverse event. CONCLUSION: Our results support the 12-month efficacy of PNS of the occipital nerves for headache pain and disability associated with chronic migraine. More emphasis on adverse event mitigation is needed in future research. TRIAL REGISTRATION: Clinical trials.gov (NCT00615342).

Peripheral nerve/field stimulation for neuropathic pain.

Peripheral nerve stimulation and peripheral nerve field stimulation are emerging as a viable neuromodulatory therapy in the treatment of refractory pain. Although the technology of percutaneous stimulation has been available for decades, recent advancements have broadened the number of indications. Success of treatment revolves around identifying the correct patient population, and the selection and placement of the appropriate electrodes and implantable pulse generators. Most results to date have come from case reports and retrospective studies. However, given the promising outcomes in reducing otherwise medically refractory pain, future randomized controlled studies are needed to assess this emerging technology.

Pathological tremor prediction using surface electromyogram and acceleration: potential use in 'ON-OFF' demand driven deep brain stimulator design.

OBJECTIVE: We present a proof of concept for a novel method of predicting the onset of pathological tremor using non-invasively measured surface electromyogram (sEMG) and acceleration from tremor-affected extremities of patients with Parkinson's disease (PD) and essential tremor (ET). APPROACH: The tremor prediction algorithm uses a set of spectral (Fourier and wavelet) and nonlinear time series (entropy and recurrence rate) parameters extracted from the non-invasively recorded sEMG and acceleration signals. MAIN RESULTS: The resulting algorithm is shown to successfully predict tremor onset for all 91 trials recorded in 4 PD patients and for all 91 trials recorded in 4 ET patients. The predictor achieves a 100% sensitivity for all trials considered, along with an overall accuracy of 85.7% for all ET trials and 80.2% for all PD trials. By using a Pearson's chi-square test, the prediction results are shown to significantly differ from a random prediction outcome. SIGNIFICANCE: The tremor prediction algorithm can be potentially used for designing the next generation of non-invasive closed-loop predictive ON-OFF controllers for deep brain stimulation (DBS), used for suppressing pathological tremor in such patients. Such a system is based on alternating ON and OFF DBS periods, an incoming tremor being predicted during the time intervals when DBS is OFF, so as to turn DBS back ON. The prediction should be a few seconds before tremor re-appears so that the patient is tremor-free for the entire DBS ON-OFF cycle and the tremor-free DBS OFF interval should be maximized in order to minimize the current injected in the brain and battery usage.

Treatment of chronic, intractable pain with a conventional implantable pulse generator: a meta-analysis of 4 clinical studies.

OBJECTIVE: To provide further short-term (6 mo) and long-term (1 y) evidence for the use of spinal cord stimulation (SCS) with a conventional implantable pulse generator in the management of chronic, intractable pain. MATERIALS AND METHODS: We conducted a meta-analysis of 4 prospective, multicenter studies that collected outcome data from patients implanted with SCS to treat chronic pain of the trunk and/or limbs (Genesis IPG system). Two of these were conducted as long-term studies lasting 1 year, and 2 as shorter term studies lasting 6 months. A total of 300 patients from 28 investigational sites were prospectively evaluated for efficacy at 3 months after implant and safety at 6 months after implant. None of the sites participated in more than one study. Outcome measures included patient-reported percent of pain relief, patient satisfaction, quality of life improvement, pain evaluation (0 to 10 rating), pain relief rating, Short-Form McGill Pain Questionnaire, visual analog scale, the Short Form-36, and the total number of adverse events (AEs). RESULTS: At 3 months after implantation of the permanent system, 75.4% of the patients (190/252) reported a 50% or greater pain relief as determined by the patient-reported degree of pain relief. Similarly, assessment of patient satisfaction with SCS therapy showed that 86.1% of patients (217/252) in all 4 studies were satisfied or very satisfied with the therapy at 3 months. In the 2 long-term studies, 80.9% of patients (140/173) were satisfied or very satisfied with the therapy at the 1-year evaluation point. Quality-of-life (QoL) data indicated that at 3 months after implant, 77.8% of patients (196/252) reported QoL as improved or greatly improved. Similarly, QoL was improved or greatly improved for 74.0% patients in the long-term study at 1 year (128/173). In the safety analysis, AEs were reviewed for all 4 studies. A total of 190 AEs were reported in 117 of 300 patients during all studies. CONCLUSIONS: This analysis provides further evidence of the safety and effectiveness of SCS in treating chronic intractable pain of the trunk and/or limbs. Specifically, it underscores a high level of effectiveness and acceptable safety concerns in the use of nonrechargeable SCS devices.