The Polyanalgesic Consensus Conference (PACC)®: Intrathecal Drug Delivery Guidance on Safety and Therapy Optimization When Treating Chronic Noncancer Pain.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians and scientists based on expertise with international representation to establish evidence-based guidance on intrathecal drug delivery in treating chronic pain. This Polyanalgesic Consensus Conference (PACC)® project, created more than two decades ago, intends to provide evidence-based guidance for important safety and efficacy issues surrounding intrathecal drug delivery and its impact on the practice of neuromodulation. MATERIALS AND METHODS: Authors were chosen on the basis of 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 PACC® last published guidelines) to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence is scant. RESULTS: The PACC® 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 PACC® recommends best practices regarding intrathecal drug delivery to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.

The Neurostimulation Appropriateness Consensus Committee (NACC)®: Recommendations for the Mitigation of Complications of Neurostimulation.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise and international representation to establish evidence-based guidance on the mitigation of neuromodulation complications. This Neurostimulation Appropriateness Consensus Committee (NACC)® project intends to update evidence-based guidance and offer expert opinion that will improve efficacy and safety. MATERIALS AND METHODS: Authors were chosen on the basis of 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 October 2023. Identified studies were graded using the United States 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 mitigation of complications associated with neurostimulation to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.

Closing the loop and raising the bar: Automated control systems in neuromodulation.

INTRODUCTION: Neuromodulation has emerged as a promising therapy for the management of chronic pain, movement disorders, and other neurological conditions. Spinal cord stimulation (SCS) is a widely used form of neuromodulation that involves the delivery of electrical impulses to the spinal cord to modulate the transmission of pain signals to the brain. In recent years, there has been increasing interest in the use of automation systems to improve the efficacy and safety of SCS. This narrative review summarizes the status of Food and Drug Administration-approved autonomous neuromodulation devices including closed loop, feedforward, and feedback systems. The review discusses the advantages and disadvantages of each system and focuses specifically on the use of these systems for SCS. It is important for clinicians to understand the expanding role of automation in neuromodulation in order to select appropriate therapies founded on automation systems to the specific needs of the patient and the underlying condition. CONCLUSION: The review also provides insights into the current state of the art in neuromodulation automation systems and discusses potential future directions for research in this field.

Diaphragm Pacing: A Safety, Appropriateness, Financial Neutrality, and Efficacy Analysis of Treating Chronic Respiratory Insufficiency.

OBJECTIVES: This study aimed to evaluate the safety and applicability of treating chronic respiratory insufficiency with diaphragm pacing relative to mechanical ventilation. MATERIALS AND METHODS: A literature review and analysis were conducted using the safety, appropriateness, financial neutrality, and efficacy principles. RESULTS: Although mechanical ventilation is clearly indicated in acute respiratory failure, diaphragm pacing improves life expectancy, increases quality of life, and reduces complications in patients with chronic respiratory insufficiency. CONCLUSION: Diaphragm pacing should be given more consideration in appropriately selected patients with chronic respiratory insufficiency.

Remote Management of Spinal Cord Stimulation Devices for Chronic Pain: Expert Recommendations on Best Practices for Proper Utilization and Future Considerations.

OBJECTIVE: Emerging spinal cord stimulation (SCS) remote monitoring and programming technologies provide a unique opportunity to address challenges of in-person visits and improve patient care, although clinical guidance on implementation is needed. The goal of this document is to establish best clinical practices for integration of remote device management into the care of patients with SCS, including remote monitoring and remote programming. MATERIALS AND METHODS: A panel of experts in SCS met in July 2022, and additional experts contributed to the development of recommendations after the meeting via survey responses and correspondence. RESULTS: Major goals of remote SCS device management were identified, including prompt identification and resolution of SCS-related issues. The panel identified metrics for remote monitoring and classified them into three categories: device-related (eg, stimulation usage); measurable physiologic or disease-related (eg, patient physical activity or pedometry); and patient-reported (eg, sleep quality and pain intensity). Recommendations were made for frequency of reviewing remote monitoring metrics, although providers should tailor follow-up to individual patient needs. Such periodic reviews of remote monitoring metrics would occur separately from automatic monitoring system notifications (if key metrics fall outside an acceptable range). The guidelines were developed in consideration of reimbursement processes, privacy concerns, and the responsibilities of the care team, industry professionals, manufacturers, patients, and caregivers. Both existing and needed clinical evidence were covered, including outcomes of interest for future studies. CONCLUSIONS: Given the expansion of SCS device capabilities, this document provides critical guidance on best practices for using remote device management, although medical necessity should drive all remote monitoring decisions, with individualized patient care. The authors also describe the potential of these emerging technologies to improve outcomes for patients with SCS, although more clinical evidence is needed.

Impact of Long-Term Evoked Compound Action Potential Controlled Closed-Loop Spinal Cord Stimulation on Sleep Quality in Patients With Chronic Pain: An EVOKE Randomized Controlled Trial Study Subanalysis.

OBJECTIVE: Spinal cord stimulation (SCS) is considered an effective interventional nonpharmacologic treatment option for several chronic pain conditions. Here we present the effects of the novel evoked compound action potential (ECAP) controlled closed-loop (ECAP-CL) SCS system on long-term sleep quality outcomes from the EVOKE study. MATERIALS AND METHODS: The EVOKE study is a double-blind, randomized, controlled clinical trial conducted at 13 sites in the United States (N = 134 patients). The clinical trial utilized SCS to manage chronic pain and compared novel ECAP-CL technology to open-loop SCS. Additionally, sleep quality data was collected using the Pittsburgh Sleep Quality Index (PSQI) at baseline and all study visits. RESULTS: The mean PSQI global score for ECAP-CL patients at baseline was 14.0 (n = 62; ± 0.5, SD 3.8), indicating poor sleep quality. Clinically meaningful and statistically significant reductions (p < 0.001) in the global PSQI scores were noted at 12 months (n = 55; 5.7 ± 0.6, SD 4.2). A total of 76.4% of ECAP-CL patients met or exceeded Minimal Clinically Important Difference from baseline in PSQI at 12 months. Additionally, 30.9% of ECAP-CL patients achieved "good sleep quality" scores (PSQI ≤ 5), and 29.1% achieved sleep quality remission. "Normative" sleep scores were observed in 29.6% of ECAP-CL patients at 12 months, and these scores were better than the US general population. Additionally, ECAP-CL patients achieved statistically significant changes from baseline (p < 0.01) across all seven subcomponent scores of PSQI at 12 months. CONCLUSIONS: ECAP-CL SCS elicits consistent neural activation of the target leading to less variability in long-term therapy delivery. In the EVOKE study, this resulted in ECAP-CL patients demonstrating clinically superior and sustained pain relief. Results from this study provide new evidence of long-term improvement in sleep quality and quantity in patients with chronic pain resulting from the use of this novel ECAP-CL SCS technology. CLINICAL TRAIL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02924129.

Holistic Treatment Response: An International Expert Panel Definition and Criteria for a New Paradigm in the Assessment of Clinical Outcomes of Spinal Cord Stimulation.

BACKGROUND: Treatment response to spinal cord stimulation (SCS) is focused on the magnitude of effects on pain intensity. However, chronic pain is a multidimensional condition that may affect individuals in different ways and as such it seems reductionist to evaluate treatment response based solely on a unidimensional measure such as pain intensity. AIM: The aim of this article is to add to a framework started by IMMPACT for assessing the wider health impact of treatment with SCS for people with chronic pain, a "holistic treatment response". DISCUSSION: Several aspects need consideration in the assessment of a holistic treatment response. SCS device data and how it relates to patient outcomes, is essential to improve the understanding of the different types of SCS, improve patient selection, long-term clinical outcomes, and reproducibility of findings. The outcomes to include in the evaluation of a holistic treatment response need to consider clinical relevance for patients and clinicians. Assessment of the holistic response combines two key concepts of patient assessment: (1) patients level of baseline (pre-treatment) unmet need across a range of health domains; (2) demonstration of patient-relevant improvements in these health domains with treatment. The minimal clinical important difference (MCID) is an established approach to reflect changes after a clinical intervention that are meaningful for the patient and can be used to identify treatment response to each individual domain. A holistic treatment response needs to account for MCIDs in all domains of importance for which the patient presents dysfunctional scores pre-treatment. The number of domains included in a holistic treatment response may vary and should be considered on an individual basis. Physiologic confirmation of therapy delivery and utilisation should be included as part of the evaluation of a holistic treatment response and is essential to advance the field of SCS and increase transparency and reproducibility of the findings.

Percutaneous image-guided lumbar decompression and interspinous spacers for the treatment of lumbar spinal stenosis: A 2-year Medicare Claims Benchmark Study.

OBJECTIVE: This prospective longitudinal study compares outcomes between Medicare beneficiaries receiving percutaneous image-guided lumbar decompression (PILD) using the mild® procedure and a control group of patients receiving interspinous spacers for the treatment of lumbar spinal stenosis (LSS) with neurogenic claudication (NC). METHODS: Patients diagnosed with LSS with NC and treated with either the mild procedure or a spacer were identified in the Medicare claims database. The incidence of harms, the rate of subsequent interventions, and the overall combined rate of harms and subsequent interventions during 2-year follow-up after the index procedure were compared between the two groups and assessed for statistical significance with p = 0.05. RESULTS: The study included 2229 patients in the mild group and 3401 patients who were implanted with interspinous spacers. The rate of harms for those treated with the mild procedure was less than half that of patients implanted with a spacer (5.6% vs. 12.1%, respectively; p < 0.0001) during 2-year follow-up. The rate of subsequent interventions was not significantly different between the two groups (24.9% and 26.1% for the mild and spacer groups, respectively; p = 0.7679). The total rate of harms and subsequent interventions for mild was found to be noninferior to spacers (p < 0.0001). CONCLUSIONS: This comprehensive study of real-world Medicare claims data demonstrated a significantly lower rate of harms for the mild procedure compared to interspinous spacers for patients diagnosed with LSS with NC, and a similar rate of subsequent interventions during 2-year follow-up.

Glossary of Neurostimulation Terminology: A Collaborative Neuromodulation Foundation, Institute of Neuromodulation, and International Neuromodulation Society Project.

OBJECTIVE: Consistent terminology is necessary to facilitate communication, but limited efforts have addressed this need in the neurostimulation community. We set out to provide a useful and updated glossary for our colleagues and prospective patients. MATERIALS AND METHODS: This collaborative effort of the Neuromodulation Foundation (NF), the Institute of Neuromodulation (IoN), and the International Neuromodulation Society (INS) expands a glossary first published in 2007 for spinal cord stimulation. Peripheral nerve, dorsal root ganglion, deep brain, and motor cortex stimulation have been added to our scope. Volunteers from the collaborating entities used a nominal group process, consensus development panels, and the Delphi technique to reach consensus on inclusion and definition of terms. We created a glossary suitable for print and for expansion on the websites of the collaborating entities, which will offer the possibility of explaining definitions for a general audience. We excluded proprietary and brand names but included terms that have attracted proprietary interest without becoming brands or trademarks. We made an effort to be inclusive while also being concise and economical with space. RESULTS: We identified and defined 91 terms for this print edition and created an accompanying list of acronyms. As appropriate, we provided figures to illustrate the definitions. CONCLUSIONS: Although we refer to the glossary presented herein as the print edition, it can of course be viewed and searched electronically. NF, IoN, and INS will continue to collaborate on expanded web editions that can include hyperlinks for internal and external navigation. We believe this glossary will benefit our growing field by facilitating communication and mitigating inappropriate use of neurostimulation terms.

Novel spinal cord stimulation system with a Battery-Free micro-implantable pulse generator.

Spinal cord stimulation (SCS) is effective for the treatment of chronic intractable pain of the trunk and limbs. The mechanism of action may be based, at least in part, upon the gate control theory; however, new waveforms may suggest other mechanisms. Although benefits of the SCS technology generally outweigh the complications associated with SCS, some complications such as infection and skin erosion over the implant can result in device removal. Additional reasons for device removal, such as pocket pain and battery depletion, have driven technological innovations including battery-free implants and device miniaturization. The neurostimulation system described here was specifically designed to address complications commonly associated with implantable batteries and/or larger implantable devices. The benefits of the small size are further augmented by a minimally invasive implant procedure. Usability data show that patients found this novel neurostimulation system to be easy to use and comfortable to wear. What is more, clinical data demonstrate that the use of this system provides statistically significant reduction in pain scores with responder rates (defined as ≥50% reduction in pain) of 78% in the low back and 83% in the leg(s). Advances in miniaturization technology arose from the considerable shrinkage of the integrated circuit, with an increase in performance, according to Moore's law (1965). However, commensurate improvements in battery technology have not maintained a similar pace. This has prompted some manufacturers to place the battery outside, against the skin, thereby allowing a massive reduction in the implant volume, with the hopes of fewer device-related complications.

Diversity of Pain Medicine Trainees and Faculty in the United States: A Cross-Sectional Analysis of Fellowship Training from 2009-2019.

OBJECTIVE: Diversity and equity in medicine remain pivotal to care delivery. Data analysis on sex and racial diversity of pain medicine fellowship trainees and faculty in the United States are scant. We sought to characterize demographic and retention patterns among pain medicine fellows and faculty, who represent the emerging chronic pain management workforce. DESIGN: cross-sectional retrospective analysis. METHOD: We conducted an analysis of data from the American Association of Medical Colleges (AAMC) and the United States Accreditation Council on Graduate Medical Education (ACGME)-approved residency and fellowship training-programs for each year from 2009 through 2019, inclusively. We compared changes in sex, racial/ethnicity composition and retention rates of fellows and faculty in the United States by practice setting. RESULTS: From 2009 to 2019, there was a 14% increase in the number of ACGME pain fellowship programs. From 2009 to 2019, the ratio of men to women pain fellows ranged from 5:1 to 3.7:1. Compared with their self-identified White peers, Asian (OR 0.44; 95% CI: 0.34-0.58), Black (OR 0.46; 95% CI: 0.30-0.72), and Native American/Alaskan Native (OR 0.26; 95% CI: 0.08-0.80) identifying individuals had significantly lower odds of being a pain fellow, P < 0.05. There was no significant difference in female (OR = 0.4, 95% CI: 0.148-1.09) and Black (OR 0.36; 95% CI: 0.11-1.12) program-directors. Pain-fellow in-state retention was 53%. CONCLUSIONS: The demographics of pain medicine training programs reflect a persistent male vs. female gap with underrepresentation of racial minorities. Further research is needed to elucidate reasons underlying these disparities.

Behavioral Survey of Effects of Pulsed Radiofrequency on Neuropathic and Nociceptive Pain in Rats: Treatment Profile and Device Implantation.

OBJECTIVES: Pulsed radiofrequency (PRF) stimulation is widely used for intractable pain; however, there is no consensus on treatment protocols and appropriate types of pain. We compared effectiveness of bipolar and unipolar PRF on neuropathic or inflammatory pains, and of targets at the dorsal root ganglion (DRG) and sciatic nerve (SN). We also examined efficacy of repetitive PRF stimulations. This preclinical study could serve as an extensive survey before human trials. MATERIALS: Spare nerve injury (SNI)-induced neuropathic pain and complete Freund's adjuvant (CFA) injection-induced inflammatory pain were used. Behavioral responses were measured using von Frey test, acetone test, and Hargreave's test at preinjury and postinjury time points. In both models, we evaluated results of DRG stimulation with unipolar PRF (45 V) versus bipolar PRF (5 V), stimulation at DRG vs. SN, and repetitive stimulations. RESULTS: Both unipolar and bipolar PRFs reduced SNI- or CFA-induced pain for a similar duration. In the SNI model, PRF-DRG had a stronger effect on tactile pain than PRF-SN but lower effect on cold allodynia, whereas in the CFA model PRF-DRG and PRF-SN showed similar effects. Repetitive PRF stimulation, by open technique or implantation method, produced analogous effect by each stimulus, and no evident analgesic tolerance or neurological deficit was shown. CONCLUSIONS: PRF temporarily attenuates neuropathic and inflammatory pain. Bipolar PRF generates significant analgesia with a much lower electrical power than unipolar PRF. Meanwhile, the minor variant effects between PRF-DRG and PRF-SN may indicate distinct mechanisms. The sustained-analgesia by repetitive treatments suggests implantation technique could be a promising choice.

Cost-Effectiveness of Dorsal Root Ganglion Stimulation or Spinal Cord Stimulation for Complex Regional Pain Syndrome.

OBJECTIVES: ACCURATE, a randomized controlled trial, compared safety and effectiveness of stimulation of the dorsal root ganglion (DRG) vs. conventional spinal cord stimulation (SCS) in complex regional pain syndrome (CRPS-I and II) of the lower extremities. This analysis compares cost-effectiveness of three modalities of treatment for CRPS, namely DRG stimulation, SCS, and comprehensive medical management (CMM). MATERIALS AND METHODS: The retrospective cost-utility analysis combined ACCURATE study data with claims data to compare cost-effectiveness between DRG stimulation, SCS, and CMM. Cost-effectiveness was evaluated using a Markov cohort model with ten-year time horizon from the U.S. payer perspective. Incremental cost-effectiveness ratio (ICER) was reported as cost in 2017 U.S. dollars per gain in quality-adjusted life years (QALYs). Willingness-to-pay thresholds of $50,000/QALY and $100,000/QALY were used to define highly cost-effective and cost-effective therapies. RESULTS: Both DRG and SCS provided an increase in QALYs (4.96 ± 1.54 and 4.58 ± 1.35 QALYs, respectively) and an increase in costs ($153,992 ± $36,651 and $128,269 ± $27,771, respectively) compared to CMM (3.58 ± 0.91 QALYs, $106,173 ± $27,005) over the ten-year model lifetime. Both DRG stimulation ($34,695 per QALY) and SCS ($22,084 per QALY) were cost-effective compared to CMM. In the base case, ICER for DRG v SCS was $68,095/QALY. CONCLUSIONS: DRG and SCS are cost-effective treatments for chronic pain secondary to CRPS-I and II compared to CMM. DRG accrued higher cost due to higher conversion from trial to permanent implant and shorter battery life, but DRG was the most beneficial therapy due to more patients receiving permanent implants and experiencing higher quality of life compared to SCS. New DRG technology has improved battery life, which we expect to make DRG more cost-effective compared to both CMM and SCS in the future.

Racial and Socioeconomic Disparities in Spinal Cord Stimulation Among the Medicare Population.

INTRODUCTION: Spinal cord stimulation (SCS) is used in the treatment of many chronic pain conditions. This study investigates racial and socioeconomic disparities in SCS among Medicare patients with chronic pain. MATERIALS AND METHODS: Patients over the age of 18 with a primary diagnosis of postlaminectomy syndrome (ICD-10 M96.1) or chronic pain syndrome (ICD-10 G89.4) were identified in the Center for Medicare and Medicaid Services (CMS) Medicare Claims Limited Data Set. We defined our outcome as SCS therapy by race and socioeconomic status. Multivariable logistic regression was used to determine the variables associated with SCS. RESULTS: We identified 1,244,927 patients treated between 2016 and 2019 with a primary diagnosis of postlaminectomy syndrome (PLS) or chronic pain syndrome (CPS). Of these patients, 59,182 (4.8%) received SCS. Multivariable logistic regression analysis revealed that, compared with White patients, Black (OR [95%CI], 0.62 [0.6-0.65], p < 0.001), Asian (0.66 [0.56-0.76], p < 0.001), Hispanic (0.86 [0.8-0.93], p < 0.001), and North American Native (0.62 [0.56-0.69], p < 0.001) patients were significantly less likely to receive SCS. In addition, patients who were dual-eligible for Medicare and Medicaid were significantly less likely to receive SCS than those eligible for Medicare only (OR = 0.38 [95% CI: 0.37-0.39], p < 0.001). CONCLUSIONS: This study suggests that racial and socioeconomic disparities exist in SCS among Medicare and Medicaid patients with PLS and CPS. Further work is required to elucidate the complex etiology underlying these findings.

ECAP-Controlled Closed-Loop Spinal Cord Stimulation Efficacy and Opioid Reduction Over 24-Months: Final Results of the Prospective, Multicenter, Open-Label Avalon Study.

INTRODUCTION: Chronic pain is a major public health concern, as is the associated use of opioid medications, highlighting the importance of alternative treatments, such as spinal cord stimulation (SCS). Here, we present the final 24-month results of the Avalon study, which investigated the use of the first closed-loop SCS system in patients with chronic pain. The system measures the evoked compound action potentials (ECAPs) elicited by each stimulus pulse and drives a feedback loop to maintain the ECAP amplitude near constant. METHODS: Fifty patients were implanted with the Evoke system (Saluda Medical) and followed over 24-months. Pain, quality of life (QOL), function, sleep, and medication use were collected at baseline and each scheduled visit. ECAP amplitudes and programming adjustments were also monitored. RESULTS: At 24 months, responder rates (≥ 50% pain reduction) and high responder rates (≥ 80% pain reduction) for overall pain were 89.5% and 68.4%, respectively, the latter up from 42.2% at 3 months. Significant improvements from baseline were observed in QOL, function, and sleep over the 24 months, including ≥ 80% experiencing a minimally important difference in QOL and > 50% experiencing a clinically significant improvement in sleep. At 24 months, 82.8% of patients with baseline opioid use eliminated or reduced their opioid intake. Over the course of the study, reprogramming need fell to an average of less than once a year. CONCLUSION: Over a 24-month period, the Evoke closed-loop SCS maintained its therapeutic efficacy despite a marked reduction in opioid use and steady decrease in the need for reprogramming.

Transcranial Magnetic Stimulation for Pain, Headache, and Comorbid Depression: INS-NANS Expert Consensus Panel Review and Recommendation.

BACKGROUND: While transcranial magnetic stimulation (TMS) has been studied for the treatment of psychiatric disorders, emerging evidence supports its use for pain and headache by stimulating either motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC). However, its clinical implementation is hindered due to a lack of consensus in the quality of clinical evidence and treatment recommendation/guideline(s). Thus, working collaboratively, this multinational multidisciplinary expert panel aims to: 1) assess and rate the existing outcome evidence of TMS in various pain/headache conditions; 2) provide TMS treatment recommendation/guidelines for the evaluated conditions and comorbid depression; and 3) assess the cost-effectiveness and technical issues relevant to the long-term clinical implementation of TMS for pain and headache. METHODS: Seven task groups were formed under the guidance of a 5-member steering committee with four task groups assessing the utilization of TMS in the treatment of Neuropathic Pain (NP), Acute Pain, Primary Headache Disorders, and Posttraumatic Brain Injury related Headaches (PTBI-HA), and remaining three assessing the treatment for both pain and comorbid depression, and the cost-effectiveness and technological issues relevant to the treatment. RESULTS: The panel rated the overall level of evidence and recommendability for clinical implementation of TMS as: 1) high and extremely/strongly for both NP and PTBI-HA respectively; 2) moderate for postoperative pain and migraine prevention, and recommendable for migraine prevention. While the use of TMS for treating both pain and depression in one setting is clinically and financially sound, more studies are required to fully assess the long-term benefit of the treatment for the two highly comorbid conditions, especially with neuronavigation. CONCLUSIONS: After extensive literature review, the panel provided recommendations and treatment guidelines for TMS in managing neuropathic pain and headaches. In addition, the panel also recommended more outcome and cost-effectiveness studies to assess the feasibility of the long-term clinical implementation of the treatment.

Paresthesia-Free Dorsal Root Ganglion Stimulation: An ACCURATE Study Sub-Analysis.

INTRODUCTION: ACCURATE, a randomized controlled trial comparing dorsal root ganglion (DRG) stimulation to spinal cord stimulation, showed that DRG stimulation is a safe and effective therapy in individuals with lower extremity chronic pain due to complex regional pain syndrome (CRPS) type I or II. Investigators noted that DRG stimulation programming could be adjusted to minimize, or eliminate, the feeling of paresthesia while maintaining adequate pain relief. The present study explores treatment outcomes for DRG subjects who were paresthesia-free vs. those who experienced the sensation of paresthesia, as well as the factors that predicted paresthesia-free analgesia. METHODS: A retrospective analysis of therapy outcomes was conducted for 61 subjects in the ACCURATE study who received a permanent DRG neurostimulator. Outcomes of subjects who were paresthesia-free were compared to those who experienced paresthesia-present therapy at 1, 3, 6, 9, and 12-month follow-ups. Predictor variables for the presence or absence of paresthesias with DRG stimulation were also explored. RESULTS: The percentage of subjects with paresthesia-free pain relief increased from 16.4% at 1-month to 38.3% at 12-months. Paresthesia-free subjects generally had similar or better outcomes for pain severity, pain interference, quality of life, and mood state as subjects with paresthesia-present stimulation. Factors that increased the odds of a subject feeling paresthesia were higher stimulation amplitudes and frequencies, number of implanted leads, and younger age. CONCLUSIONS: Some DRG subjects achieved effective paresthesia-free analgesia in the ACCURATE trial. This supports the observation that paresthesia is not synonymous with pain relief or required for optimal analgesia with DRG stimulation.

Multicenter, Randomized, Double-Blind Study Protocol Using Human Spinal Cord Recording Comparing Safety, Efficacy, and Neurophysiological Responses Between Patients Being Treated With Evoked Compound Action Potential-Controlled Closed-Loop Spinal Cord Stimulation or Open-Loop Spinal Cord Stimulation (the Evoke Study).

BACKGROUND: The spinal cord (SC) response to stimulation has yet to be studied in a pivotal clinical study. We report the study design of an ongoing multicenter, randomized, double-blind, controlled, parallel-arm study of an evoked compound action potential (ECAP) controlled closed-loop spinal cord stimulation (SCS) system, which aims to gain U.S. Food and Drug Administration approval. METHODS: This study will enroll 134 SCS candidates with chronic trunk and limb pain from up to 20 United States sites. Subjects are randomized 1:1 to receive ECAP-controlled closed-loop or open-loop, conventional SCS. The primary objective is noninferiority of closed-loop stimulation determined by the proportion of subjects with ≥50% reduction in overall trunk and limb pain and no increase in pain medications at the three-month visit. If noninferiority is met, superiority is tested. In addition, measures recommended by IMMPACT (e.g., pain intensity, functional disability, emotional functioning, quality of life, impression of change, and sleep), neurophysiological properties (e.g., SC activation, conduction velocity, chronaxie, and rheobase), and safety are analyzed. DISCUSSION: All approved SCS therapies, regardless of the presence or absence of stimulation induced paresthesias, produce fixed-output stimuli; that is, the energy delivered from the electrode array has a defined output irrespective of the neural response of SC fibers. An SCS system has been developed that directly measures the neurophysiologic activation of the SC to stimulation (i.e., ECAP amplitude) and uses this information in a feedback mechanism to produce closed-loop SCS to maintain optimal and stable activation of the SC. This study represents the first randomized, double-blind, pivotal study in the field of neuromodulation to measure SC activation in ECAP-controlled closed-loop versus open-loop stimulation and is expected to yield important information regarding differences in safety, efficacy, and neurophysiological properties. The potential clinical utility of these objective measurements of SC activation and other neurophysiological properties promises to improve outcomes of SCS for chronic pain patients.

Comparison of Paresthesia Coverage of Patient's Pain: Dorsal Root Ganglion vs. Spinal Cord Stimulation. An ACCURATE Study Sub-Analysis.

OBJECTIVES: This was a sub-analysis of the ACCURATE clinical trial that evaluated the accuracy and necessity of targeting paresthesia coverage of painful areas with dorsal root ganglion (DRG) stimulation vs. tonic spinal cord stimulation (SCS). MATERIALS AND METHODS: On diagrams of the torso and lower limbs, subjects marked where they felt pain at baseline and paresthesias at three months postimplant. Seventy-five subjects (41 DRG and 34 SCS) with diagrams of sufficient quality were scanned, digitized, and included in this analysis. Subject completed diagrams were digitized and superimposed with a grid of 1398 squares. Quantification of the percentage of bodily areas affected by pain and stimulation induced paresthesias was performed. RESULTS: The percent of painful areas covered by paresthesia was significantly lower for DRG subjects than for SCS subjects (13% vs. 28% of the painful regions, p < 0.05), possibly because significantly more DRG subjects felt no paresthesia during stimulation when compared to SCS subjects (13/41 DRG vs. 3/34 SCS) (p < 0.05). The amount of paresthesia produced outside the painful areas (unrequired paresthesia) was significantly lower in DRG subjects than that of SCS subjects. On average, the percent of unrequired paresthesia was only 20% of the subjects' total painful body surface area in the DRG group compared to 210% in the SCS group (p < 0.01). CONCLUSIONS: The results of this ACCURATE study sub-analysis show that DRG stimulation produces paresthesias, on average, that are less frequent, less intense, with a smaller footprint on the body and less dependent on positional changes.