A Definition of Neuromodulation and Classification of Implantable Electrical Modulation for Chronic Pain.

OBJECTIVES: Neuromodulation therapies use a variety of treatment modalities (eg, electrical stimulation) to treat chronic pain. These therapies have experienced rapid growth that has coincided with escalating confusion regarding the nomenclature surrounding these neuromodulation technologies. Furthermore, studies are often published without a complete description of the effective stimulation dose, making it impossible to replicate the findings. To improve clinical care and facilitate dissemination among the public, payors, research groups, and regulatory bodies, there is a clear need for a standardization of terms. APPROACH: We formed an international group of authors comprising basic scientists, anesthesiologists, neurosurgeons, and engineers with expertise in neuromodulation. Because the field of neuromodulation is extensive, we chose to focus on creating a taxonomy and standardized definitions for implantable electrical modulation of chronic pain. RESULTS: We first present a consensus definition of neuromodulation. We then describe a classification scheme based on the 1) intended use (the site of modulation and its indications) and 2) physical properties (waveforms and dose) of a neuromodulation therapy. CONCLUSIONS: This framework will help guide future high-quality studies of implantable neuromodulatory treatments and improve reporting of their findings. Standardization with this classification scheme and clear definitions will help physicians, researchers, payors, and patients better understand the applications of implantable electrical modulation for pain and guide informed treatment decisions.

WIKISTIM.org: An On-Line Database of Published Neurostimulation Studies.

INTRODUCTION: Primary data reported in scientific publications provide guidance for improving patient care, expanding indications, identifying research gaps, educating patients, justifying reimbursement, and gaining regulatory approval. Finding and analyzing pertinent publications among the huge volume noted in databases such as PUBMED, however, costs time and effort. This situation demands innovative ways to locate citations of (and the possibility of abstracting data from) papers reporting primary findings. METHODS: We created WIKISTIM.org, a searchable easily navigated website, to meet this challenge in our field and devised a taxonomy of data categories specific for various stimulation targets for extracting and posting primary data. We included a discussion section unlimited by time or space to overcome limits posed by traditional letters to the editor. RESULTS: Registrants can download single or multiple citations from search results or from the list of papers (sortable by author, title, publication, and year) into a single table. The downloadable data category lists are used to submit completed data entry sheets for upload and for evidence-based comparison across studies as well as for study design, manuscript preparation, and peer review. Registration for WIKISTIM access continues to grow as do the curated citation lists, which are updated monthly and are comprehensive for deep brain stimulation, dorsal root ganglion stimulation, gastric electric stimulation, spinal cord stimulation, and sacral nerve stimulation. CONCLUSIONS: Most WIKISTIM entries are limited to citation information and links to published abstracts. As the number of completed datasheets and of stimulation target sections increase, the value of WIKISTIM will increase.

The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the Neuromodulation Appropriateness Consensus Committee.

INTRODUCTION: The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications. METHODS: The NACC used literature reviews, expert opinion, clinical experience, and individual research. Authors consulted the Practice Parameters for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain (2006), systematic reviews (1984 to 2013), and prospective and randomized controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google Scholar. RESULTS: Neurostimulation is relatively safe because of its minimally invasive and reversible characteristics. Comparison with medical management is difficult, as patients considered for neurostimulation have failed conservative management. Unlike alternative therapies, neurostimulation is not associated with medication-related side effects and has enduring effect. Device-related complications are not uncommon; however, the incidence is becoming less frequent as technology progresses and surgical skills improve. Randomized controlled studies support the efficacy of spinal cord stimulation in treating failed back surgery syndrome and complex regional pain syndrome. Similar studies of neurostimulation for peripheral neuropathic pain, postamputation pain, postherpetic neuralgia, and other causes of nerve injury are needed. International guidelines recommend spinal cord stimulation to treat refractory angina; other indications, such as congestive heart failure, are being investigated. CONCLUSIONS: Appropriate neurostimulation is safe and effective in some chronic pain conditions. Technological refinements and clinical evidence will continue to expand its use. The NACC seeks to facilitate the efficacy and safety of neurostimulation.

The appropriate use of neurostimulation: avoidance and treatment of complications of neurostimulation therapies for the treatment of chronic pain. Neuromodulation Appropriateness Consensus Committee.

INTRODUCTION: The International Neuromodulation Society (INS) has determined that there is a need for guidance regarding safety and risk reduction for implantable neurostimulation devices. The INS convened an international committee of experts in the field to explore the evidence and clinical experience regarding safety, risks, and steps to risk reduction to improve outcomes. METHODS: The Neuromodulation Appropriateness Consensus Committee (NACC) reviewed the world literature in English by searching MEDLINE, PubMed, and Google Scholar to evaluate the evidence for ways to reduce risks of neurostimulation therapies. This evidence, obtained from the relevant literature, and clinical experience obtained from the convened consensus panel were used to make final recommendations on improving safety and reducing risks. RESULTS: The NACC determined that the ability to reduce risk associated with the use of neurostimulation devices is a valuable goal and possible with best practice. The NACC has recommended several practice modifications that will lead to improved care. The NACC also sets out the minimum training standards necessary to become an implanting physician. CONCLUSIONS: The NACC has identified the possibility of improving patient care and safety through practice modification. We recommend that all implanting physicians review this guidance and consider adapting their practice accordingly.

Spinal cord stimulation versus re-operation in patients with failed back surgery syndrome: an international multicenter randomized controlled trial (EVIDENCE study).

OBJECTIVE: This paper presents the protocol of the EVIDENCE study, a multicenter multinational randomized controlled trial to assess the effectiveness and cost-effectiveness of spinal cord stimulation (SCS) with rechargeable pulse generator versus re-operation through 36-month follow-up in patients with failed back surgery syndrome. STUDY DESIGN: Study subjects have neuropathic radicular leg pain exceeding or equaling any low back pain and meet specified entry criteria. One-to-one randomization is stratified by site and by one or more prior lumbosacral operations. The sample size of 132 subjects may be adjusted to between 100 and 200 subjects using a standard adaptive design statistical method with pre-defined rules. Crossover treatment is possible. Co-primary endpoints are proportion of subjects reporting ≥ 50% leg pain relief without crossover at 6 and at 24 months after SCS screening trial or re-operation. Insufficient pain relief constitutes failure of randomized treatment, as does crossover. Secondary endpoints include cost-effectiveness; relief of leg, back, and overall pain; change in disability and quality of life; and rate of crossover. We are collecting data on subject global impression of change, patient satisfaction with treatment, employment status, pain/paresthesia overlap, SCS programming, and adverse events. DISCUSSION: As the first multicenter randomized controlled trial of SCS versus re-operation and the first to use only rechargeable SCS pulse generators, the EVIDENCE study will provide up-to-date evidence on the treatment of failed back surgery syndrome.

Incidence and avoidance of neurologic complications with paddle type spinal cord stimulation leads.

INTRODUCTION: While reference is frequently made to the risk of spinal cord or nerve root injury with the surgical implantation of paddle type spinal cord stimulation (SCS) electrodes, data are lacking on the frequency, causes, and prevention of these complications. METHODS: To determine the incidence and frequency of neurologic complications, we performed 1) a comprehensive analysis of the literature to determine the incidence of complications that have caused or could lead to neurologic injury; 2) an analysis of the US Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) data base; and 3) an investigation of manufacturers' data on surgically implanted paddle electrodes. We then convened an expert panel of neurosurgeons experienced in the surgical implantation of paddle electrodes to provide recommendations to minimize the risk of neurologic injury. RESULTS: The scientific literature describes the breadth of neurologic complications that can result from SCS electrode implantation but does not provide interpretable data with respect to the incidence and frequency of these complications. The MAUDE data base is not constructed to be sensitive or specific enough to provide these critical data. Primary data show a risk of neurologic injury from implantation of paddle electrodes below 0.6%. DISCUSSION: Preoperative, intraoperative, and postoperative measures to further minimize this risk are described. CONCLUSIONS: This investigation, the first comprehensive evaluation of the incidence and frequency of neurologic injury as a result of SCS paddle electrode implantation, suggests that neurologic injury is a rare, but serious, complication of SCS. The incidence of these complications should be decreased by the adoption of approaches that improve procedural safety and by careful patient follow-up and complication management. Physicians should be aware of these approaches and take every precaution to reduce the risk of neurologic injury. Physicians also should report any adverse event leading to injury or death and work together to improve access to these data.

The cost-effectiveness of spinal cord stimulation in the treatment of failed back surgery syndrome.

OBJECTIVES: Healthcare policy makers and payers require cost-effectiveness evidence to inform their treatment funding decisions. Thus, in 2008, the United Kingdom's National Institute of Health and Clinical Excellence analyzed the cost effectiveness of spinal cord stimulation (SCS) compared with conventional medical management (CMM) and with reoperation and recommended approval of SCS in selected patients with failed back surgery syndrome (FBSS). We present previously unavailable details of the National Institute of Health and Clinical Excellence analysis and an analysis of the impact on SCS cost effectiveness of rechargeable implanted pulse generators (IPGs). METHODS: We used a decision analytic model to examine the cost effectiveness of SCS versus CMM and versus reoperation in patients with FBSS. We also modeled the impact of nonrechargeable versus rechargeable IPGs. RESULTS: The incremental cost-effectiveness of SCS compared with CMM was pound5624 per quality-adjusted life year, with 89% probability that SCS is cost effective at a willingness to pay threshold of pound20,000. Compared with reoperation, the incremental cost-effectiveness of SCS was pound6392 per quality-adjusted life year, with 82% probability of cost-effectiveness at the pound20,000 threshold. When the longevity of an IPG is 4 years or less, a rechargeable (and initially more expensive) IPG is more cost-effective than a nonrechargeable IPG. DISCUSSION: In selected patients with FBSS, SCS is cost effective both as an adjunct to CMM and as an alternative to reoperation. Despite their initial increased expense, rechargeable IPGs should be considered when IPG longevity is likely to be short.

The effects of spinal cord stimulation in neuropathic pain are sustained: a 24-month follow-up of the prospective randomized controlled multicenter trial of the effectiveness of spinal cord stimulation.

OBJECTIVE: After randomizing 100 failed back surgery syndrome patients to receive spinal cord stimulation (SCS) plus conventional medical management (CMM) or CMM alone, the results of the 6-month Prospective Randomized Controlled Multicenter Trial of the Effectiveness of Spinal Cord Stimulation (i.e., PROCESS) showed that SCS offered superior pain relief, health-related quality of life, and functional capacity. Because the rate of crossover favoring SCS beyond 6 months would bias a long-term randomized group comparison, we present all outcomes in patients who continued SCS from randomization to 24 months and, for illustrative purposes, the primary outcome (>50% leg pain relief) per randomization and final treatment. METHODS: Patients provided data on pain, quality of life, function, pain medication use, treatment satisfaction, and employment status. Investigators documented adverse events. Data analysis included inferential comparisons and multivariate regression analyses. RESULTS: The 42 patients continuing SCS (of 52 randomized to SCS) reported significantly improved leg pain relief (P < 0.0001), quality of life (P

Spinal cord stimulation versus conventional medical management for neuropathic pain: a multicentre randomised controlled trial in patients with failed back surgery syndrome.

Patients with neuropathic pain secondary to failed back surgery syndrome (FBSS) typically experience persistent pain, disability, and reduced quality of life. We hypothesised that spinal cord stimulation (SCS) is an effective therapy in addition to conventional medical management (CMM) in this patient population. We randomised 100 FBSS patients with predominant leg pain of neuropathic radicular origin to receive spinal cord stimulation plus conventional medical management (SCS group) or conventional medical management alone (CMM group) for at least 6 months. The primary outcome was the proportion of patients achieving 50% or more pain relief in the legs. Secondary outcomes were improvement in back and leg pain, health-related quality of life, functional capacity, use of pain medication and non-drug pain treatment, level of patient satisfaction, and incidence of complications and adverse effects. Crossover after the 6-months visit was permitted, and all patients were followed up to 1 year. In the intention-to-treat analysis at 6 months, 24 SCS patients (48%) and 4 CMM patients (9%) (p<0.001) achieved the primary outcome. Compared with the CMM group, the SCS group experienced improved leg and back pain relief, quality of life, and functional capacity, as well as greater treatment satisfaction (p

Spinal cord stimulation versus reoperation for failed back surgery syndrome: a cost effectiveness and cost utility analysis based on a randomized, controlled trial.

OBJECTIVE: We analyzed the cost-effectiveness and cost-utility of treating failed back-surgery syndrome using spinal cord stimulation (SCS) versus reoperation. MATERIALS AND METHODS: A disinterested third party collected charge data for the first 42 patients in a randomized controlled crossover trial. We computed the difference in cost with regard to success (cost-effectiveness) and mean quality-adjusted life years (cost-utility). We analyzed the patient-charge data with respect to intention to treat (costs and outcomes as a randomized group), treated as intended (costs as randomized; crossover failure assigned to a randomized group), and final treatment costs and outcomes. RESULTS: By mean 3.1-year follow-up, 13 of 21 patients (62%) crossed from reoperation versus 5 of 19 patients (26%) who crossed from SCS (P < 0.025) [corrected]. The mean cost per success was US $117,901 for crossovers to SCS. No crossovers to reoperation achieved success despite a mean per-patient expenditure of US $260,584. The mean per-patient costs were US $31,530 for SCS versus US $38,160 for reoperation (intention to treat), US $48,357 for SCS versus US $105,928 for reoperation (treated as intended), and US $34,371 for SCS versus US $36,341 for reoperation (final treatment). SCS was dominant (more effective and less expensive) in the incremental cost-effectiveness ratios and incremental cost-utility ratios. A bootstrapped simulation for incremental costs and quality-adjusted life years confirmed SCS's dominance, with approximately 72% of the cost results occurring below US policymakers' "maximum willingness to pay" threshold. CONCLUSION: SCS was less expensive and more effective than reoperation in selected failed back-surgery syndrome patients, and should be the initial therapy of choice. SCS is most cost-effective when patients forego repeat operation. Should SCS fail, reoperation is unlikely to succeed.