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

Disease applications of spinal cord stimulation: Chronic nonmalignant pain.

Neuropathic pain is a chronic condition representing a significant burden for society. It is estimated 1 out of 10 people over the age of 30 that in the US have been diagnosed with neuropathic pain. Most of the available treatments for neuropathic pain have moderate efficacy over time which limit their use; therefore, other therapeutic approaches are needed for patients. Spinal cord stimulation is an established and cost-effective modality for treating severe chronic pain. In this article we will review the current approved indications for the use of spinal cord stimulation in the US and the novel therapeutic options which are now available using this therapy

Using evoked compound action potentials to quantify differential neural activation with burst and conventional, 40 Hz spinal cord stimulation in ovines.

UNLABELLED: Unlike conventional dorsal spinal cord stimulation (SCS)-which uses single pulses at a fixed rate-burst SCS uses a fixed-rate, five-pulse stimuli cluster as a treatment for chronic pain; mechanistic explanations suggest burst SCS differentially modulate the medial and lateral pain pathways vs conventional SCS. Neural activation differences between burst and conventional SCS are quantifiable with the spinal-evoked compound action potential (ECAP), an electrical measure of synchronous neural activation. METHODS: We implanted 7 sheep with a dorsal stimulation lead at T9/T10, a dorsal ECAP sensing lead at T6/T7, and a lead also at T9/T10 but adjacent to the anterolateral system (ALS). Both burst and conventional SCS with stimulation amplitudes up to the visual motor threshold (vMT) were delivered to 3 different dorsal spinal locations, and ECAP thresholds (ECAPTs) were calculated for all combinations. Then, changes in ALS activation were assessed with both types of SCS. RESULTS: Evoked compound action potential thresholds and vMTs were significantly higher (P < 0.05) with conventional vs burst SCS, with no statistical difference (P > 0.05) among stimulation sites. However, the vMT-ECAPT window (a proxy for the useable therapeutic dosing range) was significantly wider (P < 0.05) with conventional vs burst SCS. No significant difference (P > 0.05) in ALS activation was noted between conventional and burst SCS. CONCLUSION: When dosed equivalently, no differentially unique change in ALS activation results with burst SCS vs conventional SCS; in addition, sub-ECAPT burst SCS results in no discernable excitability changes in the neural pathways feeding pain relevant supraspinal sites

The Impact of Age on the Outcomes of Minimally Invasive Lumbar Decompression for Lumbar Spinal Stenosis.

BACKGROUND AND PURPOSE: Minimally invasive lumbar decompression (mild ®) is an effective long-term therapy for patients with symptomatic lumbar spinal stenosis (LSS) resulting primarily from hypertrophic ligamentum flavum (HLF). Most subjects in clinical studies of the mild procedure have been older adults (age≥65). While the incidence of LSS increases with age, a substantial number of adults (age<65) also suffer from neurogenic claudication secondary to HLF. In this report, outcomes of mild were compared between adults and older adults. PATIENTS AND METHODS: All prospective studies of the mild procedure with a 1-year follow-up completed since the beginning of 2012 that allowed the inclusion of adult patients of all ages were reviewed. Outcomes of visual analog scale (VAS), Oswestry Disability Index (ODI), Pain Disability Index (PDI), Roland Morris Low Back Pain and Disability Questionnaire (RMQ), standing time and walking distance were compared for adults and older adults. RESULTS: Four studies met the inclusion criteria, resulting in an analysis of 49 adults and 160 older adults. Patients in both age groups experienced significant mean improvements in all but one outcome measure at 6- and 12-month follow-up. Differences between the two age groups in all scores at 6 and 12 months were not statistically significant. CONCLUSION: Analysis of the four studies indicated that symptom improvements for adults and older adults were significant from baseline, and no statistically significant difference was observed between the two age groups. These results illustrate that mild can be an effective treatment for LSS due primarily to HLF, regardless of the adult patient age

O129 / #846 GLOSSARY OF NEUROSTIMULATION TERMINOLOGY: A COLLABORATIVE NEUROMODULATION FOUNDATION, INSTITUTE OF NEUROMODULATION, AND INTERNATIONAL NEUROMODULATION SOCIETY PROJECT: TRACK 3: VAGUS NERVE STIMULATION / TOOLS TO INFORM PATIENT CARE

Introduction: Consistent terminology is necessary to facilitate communication, but only 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 / 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 (1,2). 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 a print edition of the glossary and created an accompanying list of acronyms. As appropriate, we provided figures to illustrate the definitions. Discussion: The field of neuromodulation requires a specialized vocabulary. Growth in the field, however, has led to inappropriate use of terminology. For example: 1) tonic” refers to a continuous sequence of pulses with invariant amplitude, duration, and frequency/repetition rate and should not be used to distinguish between low and high frequency stimulation; 2) percutaneous trans-spinal placement of dorsal root ganglion stimulating electrodes does not result in SCS of the DRG ; and 3) nonlinear burst stimulation” is not useful in distinguishing between forms of burst stimulation. We excluded trademarked terms but included some ( central point of stimulation” density” and dose ) that have received attention from proprietary interests. The need for a glossary to address misguided usage and spelling has long been apparent. An example is the awkward attempt to create a plural for paresthesia” (“paresthesias” or even “paresthesiae”). Like anesthesia” (but unlike data ), paresthesia” is both singular and plural. Conclusions: The edition of our glossary soon to be published in the journal Neuromodulation can of course be viewed and searched electronically. NF, IoN, and INS will continue to collaborate on expanded Web editions, which 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

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

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

Real World Clinical Utility of Neurophysiological Measurement Utilizing Closed-Loop Spinal Cord Stimulation in a Chronic Pain Population: The ECAP Study Protocol.

BACKGROUND: Spinal cord stimulation (SCS) is an established chronic pain treatment, but the effectiveness of traditional, open-loop paradigms has been plagued by variable sustainability in a real-world setting. A new approach, utilizing evoked compound action potential (ECAP) controlled closed-loop (CL) SCS, continuously monitors spinal cord activation and automatically adjusts the stimulation amplitude of every pulse, maintaining stimulation at the prescribed ECAP level through this continual feedback mechanism. Recent studies demonstrated the long-term safety and efficacy of ECAP-controlled CL-SCS. Here, we report the design of a prospective, multicenter, single-arm feasibility study to characterize clinical outcomes in a real-world chronic pain population utilizing ECAP-controlled CL-SCS. Objective neurophysiological measurements such as device performance and patient therapy compliance, will be analyzed against baseline biopsychosocial assessments, to explore the clinical utility of these objective physiologic biomarkers in patient phenotyping. METHODS: This study will enroll up to 300 subjects with chronic, intractable trunk and/or limb pain in up to 25 United States investigation sites. Subjects meeting eligibility criteria will undergo a trial procedure and a permanent implant following a successful trial. Neurophysiological measurements (measured in-clinic and continuously during home use) and clinical outcomes including pain, quality-of-life, psychological, emotional, and functional assessments will be collected at baseline, trial end, and up to 24-months post-implantation. DISCUSSION: Associations between objective neurophysiological data, clinical evaluation and patient-reported outcomes may have important clinical and scientific implications. They may provide novel insights about the chronic pain pathophysiology, its modulation during CL-SCS, and identification of pain phenotypes and/or mechanisms associated with treatment response during SCS trials and long-term therapy. Data from the ECAP study could lead to improvements in diagnosis, assessment, patient identification and management of chronic pain. It could also provide the foundation for development of a new SCS treatment approach customized by the patients pain phenotype, unique neurophysiology, and disease severity

Sustained Long-Term Outcomes With Closed-Loop Spinal Cord Stimulation: 12-Month Results of the Prospective, Multicenter, Open-Label Avalon Study.

BACKGROUND: Spinal cord stimulation (SCS) activates the dorsal column fibers using electrical stimuli. Current SCS systems function in fixed-output mode, delivering the same stimulus regardless of spinal cord (SC) activation. OBJECTIVE: To present long-term outcomes of a novel closed-loop SCS system that aims to maintain the SC activation near a set target level and within a therapeutic window for each patient. SC activation is measured through the evoked compound action potential (ECAP) generated by each stimulus pulse. METHODS: Fifty patients with lower back and/or leg pain who were successfully trialed received a permanent system (Evoke; Saluda Medical, Sydney, Australia). Ratings of pain (visual analog scale), quality of life, function, sleep, and medication use were collected at baseline and at each visit. SC activation levels were reported in summary statistics. The therapeutic window for each individual patient was defined as the range of ECAP amplitudes between sensation threshold and uncomfortably strong stimulation. RESULTS: At 12 mo, the proportion of patients with ≥50% relief was 76.9% (back), 79.3% (leg), and 81.4% (overall), and the proportion with ≥80% pain relief was 56.4% (back), 58.6% (leg), and 53.5% (overall). Patients spent a median of 84.9% of their time with stimulation in their therapeutic window, and 68.8% (22/32) eliminated or reduced their opioid intake. Statistically significant improvements in secondary outcomes were observed. CONCLUSION: The majority of patients experienced more than 80% pain relief with stable SC activation, as measured by ECAP amplitude at 12 mo, providing evidence for the long-term effectiveness of the Evoke closed-loop SCS system

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