Primary 3-Month Outcomes of a Double-Blind Randomized Prospective Study (The QUEST Study) Assessing Effectiveness and Safety of Novel High-Frequency Electric Nerve Block System for Treatment of Post-Amputation Pain.

Purpose: This multicenter, randomized, double-blinded, active sham-controlled pivotal study was designed to assess the efficacy and safety of high-frequency nerve block treatment for chronic post-amputation and phantom limb pain. Patients and Methods: QUEST enrolled 180 unilateral lower-limb amputees with severe post-amputation pain, 170 of whom were implanted with the Altius device, were randomized 1:1 to active-sham or treatment groups and reached the primary endpoint. Responders were those subjects who received ≥50% pain relief 30 min after treatment in ≥50% of their self-initiated treatment sessions within the 3-month randomized period. Differences between the active treatment and sham control groups as well as numerous secondary outcomes were determined. Results: At 30-min, (primary outcome), 24.7% of the treatment group were responders compared to 7.1% of the control group (p=0.002). At 120-minutes following treatment, responder rates were 46.8% in the Treatment group and 22.2% in the Control group (p=0.001). Improvement in Brief Pain Inventory interference score of 2.3 ± 0.29 was significantly greater in treatment group than the 1.3 ± 0.26-point change in the Control group (p = 0.01). Opioid usage, although not significantly different, trended towards a greater reduction in the treatment group than in the control group. The incidence of adverse events did not differ significantly between the treatment and control groups. Conclusion: The primary outcomes of the study were met, and the majority of Treatment patients experienced a substantial improvement in PAP (regardless of meeting the study definition of a responder). The significant in PAP was associated with significantly improved QOL metrics, and a trend towards reduced opioid utilization compared to Control. These data indicate that Altius treatment represents a significant therapeutic advancement for lower-limb amputees suffering from chronic PAP.

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.

Persistent Spinal Pain Syndrome: A Proposal for Failed Back Surgery Syndrome and ICD-11.

OBJECTIVE: For many medical professionals dealing with patients with persistent pain following spine surgery, the term Failed back surgery syndrome (FBSS) as a diagnostic label is inadequate, misleading, and potentially troublesome. It misrepresents causation. Alternative terms have been suggested, but none has replaced FBSS. The International Association for the Study of Pain (IASP) published a revised classification of chronic pain, as part of the new International Classification of Diseases (ICD-11), which has been accepted by the World Health Organization (WHO). This includes the term Chronic pain after spinal surgery (CPSS), which is suggested as a replacement for FBSS. METHODS: This article provides arguments and rationale for a replacement definition. In order to propose a broadly applicable yet more precise and clinically informative term, an international group of experts was established. RESULTS: 14 candidate replacement terms were considered and ranked. The application of agreed criteria reduced this to a shortlist of four. A preferred option-Persistent spinal pain syndrome-was selected by a structured workshop and Delphi process. We provide rationale for using Persistent spinal pain syndrome and a schema for its incorporation into ICD-11. We propose the adoption of this term would strengthen the new ICD-11 classification. CONCLUSIONS: This project is important to those in the fields of pain management, spine surgery, and neuromodulation, as well as patients labeled with FBSS. Through a shift in perspective, it could facilitate the application of the new ICD-11 classification and allow clearer discussion among medical professionals, industry, funding organizations, academia, and the legal profession.

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.

Intraoperative electromyography as an adjunct to sacral neuromodulation for chronic pelvic pain.

OBJECTIVE: Sacral neuromodulation is an established technique for the treatment of chronic intractable pelvic and anorectal pain. Stimulation of sacral roots S2-4 is typically associated with therapeutic paresthesia, while stimulation of the S1 nerve root causes unwanted leg paresthesia. Here we describe and evaluate the use of intraoperative electromyography (EMG) of the gastrocnemius, foot intrinsic muscles, and anal sphincter as an adjunct to epidural stimulator placement. MATERIALS AND METHODS: Two female patients with intractable pelvic pain underwent implantation of sacral epidural paddles with intraoperative EMG. These cases were retrospectively reviewed to evaluate intraoperative EMG activation and therapeutic paresthesia. RESULTS: We found cephalad-to-caudal transitions in EMG activation with stimulation: medial gastrocnemius to foot intrinsics to anal sphincter. Coactivation of foot intrinsic muscles with anal sphincter and absence of medial gastrocnemius stimulation correlated with therapeutic perineal paresthesia. CONCLUSIONS: Intraoperative EMG of the gastrocnemius, foot intrinsics, and anal sphincter may be a useful adjunct to sacral stimulation for pelvic pain.

Principles of cord activation during spinal cord stimulation.

OBJECTIVES: This study aims to review some of the basic principles of extracellular electrical stimulation used in spinal cord stimulation therapy for intractable pain. MATERIALS AND METHODS: Spinal cord stimulation has been used therapeutically for more than 40 years. We present the basic principles of extracellular stimulation on which the therapy is based, describe electrode operation and current configurations, and explain the implications of these technological advances for the clinical application of spinal cord stimulation. RESULTS: Computational studies of coupled electric field and neuron models have significantly advanced our understanding of the therapeutic effects of neurostimulation. Neurostimulation is intended to obtain maximal selectivity of desired neural elements while avoiding those resulting in side-effects. Preferential stimulation of the dorsal columns is achieved with a narrow spacing between electrodes using bipolar or tripolar electrode configurations. Stimulus parameters such as amplitude and pulse width may be used to selectively control which neuronal elements are excited during stimulation. CONCLUSIONS: A better understanding of the interaction between electric fields and the targeted neural elements may guide the selection of stimulation parameters in contemporary neurostimulators and lead to continuing advances in engineering solutions for therapeutic spinal cord stimulation.

Using peripheral nerve stimulation (PNS) to treat neuropathic pain: a clinical series.

OBJECTIVE: We examined the efficacy of peripheral nerve stimulation (PNS) in treating neuropathic and causalgic pain, with a stimulation system specifically designated for PNS itself. MATERIALS AND METHODS: A total of 15 patients were treated between January 2011 and March 2012. The percutaneous lead was implanted on the nerves, exposing it on the electrical nerve stimulation (ENS) guide. The average numeric rating scale (NRS) preimplant was 8.46, and the oxycodone intake was 90 mg/day. RESULTS: Of the 15 patients, 3 failed the trial phase and 12 were implanted with a permanent pulse generator (Lightpulse 100, Neurimpulse, Rubano, PD, Italy). At an average of 9.3 months of follow-up, the average NRS score was 3.46 (p < 0.001), and the average Likert scale score at 7 points was 5.91. Nine patients were working prior to their injuries, seven of whom returned to work after receiving an implant. The average oxycodone consumption decreased to 30 mg/day, and the pregabalin dosage decreased to 75 mg/day. CONCLUSION: Our study results confirm that PNS is an effective modality in managing severe neuropathic and intractable pain following multiple joint surgeries that are complicated by causalgic pain.

Peripheral nerve field stimulation for the management of localized chronic intractable back pain: results from a randomized controlled study.

OBJECTIVES: Improved device technology has caused a renewed interest in peripheral nerve field stimulation (PNfS). This study sought to obtain preliminary estimates of the safety and efficacy of PNfS in patients with localized chronic intractable pain of the back. MATERIALS AND METHODS: This Institutional Review Board-approved, prospective, randomized, controlled, crossover study consisted of two phases. During phase I, patients rotated through four stimulation groups (minimal, subthreshold, low frequency, and standard stimulation). If a 50% reduction in pain was achieved during any of the three active stimulation groups (responder), the patient proceeded to phase II, which began with implant of the permanent system and lasted 52 weeks. The primary endpoint was a reduction in pain, assessed by the visual analog scale (VAS). Analysis of variance, including the effects of patient, treatment, and study period, was used for phase I results. Phase II results were analyzed by paired t-tests. RESULTS: A total of 44 patients were enrolled at five sites. Of these patients, 32 were implanted with a trial system and 30 completed phase I. During phase I, there were significant differences in mean VAS scores between minimal stimulation and subthreshold stimulation (p = 0.003), low frequency stimulation (p < 0.001), and standard stimulation (p < 0.001). Twenty-four patients were classified as responders to the therapy, and 23 patients received permanent system placement. Significant differences in VAS scores were observed between baseline and all follow-up visits during phase II (p < 0.001) CONCLUSIONS: The results provide evidence to support safety and effectiveness of PNfS as an aid in the management of chronic, localized back pain.

Spinal cord stimulation (SCS) in conjunction with peripheral nerve field stimulation (PNfS) for the treatment of complex pain in failed back surgery syndrome (FBSS).

BACKGROUND: Failed back surgery syndrome (FBSS) is a well-defined pathologic condition observed over many years. DESIGN: We have investigated the effect of spinal cord stimulation (SCS) with peripheral nerve field stimulation (PNfS) in eight patients with FBSS. OUTCOME MEASURE: The following parameters were collected and analyzed: The pain intensity score on a 0-10 numbering rating scale (NRS), the psychologic profile with Beck Depression Inventory (BDI), the pain quality with McGill Pain Questionnaire-short form (MGPQ-sf), the back pain with Oswestry scale score (OS), and the health general quality pattern with QualityMetric's SF-36v2(®) Health Survey. PATIENTS: Eight patients with low back and radicular pain in FBSS are reported. The mean duration of pain was 6.7 months, and the mean NRS score was 9.5, BDI 28.8, MGPQ-sf 16.8, OS 44.5, and SF-36 score was 72.8. The average drug intake of opioids was 250 mg/day. INTERVENTION: In six patients, two octopolar leads were placed in epidural space at D7-D8 and D8-D9, in conjunction with two octopolar leads placed in lumbar-sacral subcutaneous space (Precision System, Boston Scientific, Valencia, CA, USA), and in two patients, a two tetrapolar leads was placed in epidural space at D8-D9 with two tetrapolar leads (Pisces Quad, Plus, Medtronic Inc., Minneapolis, MN, USA) placed in lumbar-sacral subcutaneous space (Restore Ultra, Medtronic Inc., Minneapolis, MN, USA). RESULTS: After one year mean of follow-up, the mean NRS score was 4, BDI 8, MGPQ-sf 5, OS 21, and the SF-36 score was increased at 108.5. The mean drug intake of opioids was decreased at 20 mg/day. CONCLUSION: The combination of SCS and PNfS, using the latest rechargeable systems, may be a valid therapeutic strategy in FBSS.

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.

Peripheral subcutaneous stimulation for intractable abdominal pain.

Peripheral subcutaneous stimulation has been utilized for a variety of painful conditions affecting the abdominal wall, including sequelae of hernia repair, painful surgical scars, ilio-inguinal neuritis. It has also occasionally been shown to be effective in patients with intractable abdominal visceral pain. Since this is a very recent modality, no large series or prospective studies exist. The results, however, are promising and certainly warrant further investigation.

Spinal cord stimulation as alternative treatment for chronic post-herniorrhaphy pain.

OBJECTIVE: Our goal was to determine the efficacy of spinal cord stimulation for patients with intractable post-herniorrhaphy pain which conventional treatment failed to ameliorate. PROCEDURE: The patients underwent an uneventful spinal cord stimulator (SCS) trial with percutaneous placement of two eight-electrode epidural leads (Medtronic Inc, Minneapolis, MN, USA) to level T7-T8-T9. RESULTS: Upon experiencing excellent pain relief over the next two days during the trial, the patients were implanted with permanent leads and rechargeable or non-rechargeable generators two to four weeks later and reported sustained pain relief during following 12 months after implantation. CONCLUSION: We conclude that SCS offers an alternative treatment option for intractable post-herniorrhaphy pain. This type of treatment should be considered for use in a select group of patients when all conventional treatments failed.

Successful treatment of chronic neuropathic pain with subcutaneous peripheral nerve stimulation: four case reports.

Introduction. Chronic pain is a prevalent medical condition in the general population and is one of the most common reasons patients visit their primary care doctors. When the pain is resistant to the common treatment modalities, it presents a challenge for the physician and may have profound consequences for the quality of life of the patient. Methods. We present four case reports in which subcutaneous peripheral nerve stimulation was successfully used to treat chronic neuropathic pain after all other treatment efforts had failed. Results. In all cases, the patients underwent a trial of peripheral nerve stimulation with good results. The patients reported decreased use of pain medications, increased quality of life, and high satisfaction with the procedure results. Conclusion. The use of subcutaneous peripheral nerve stimulation as a viable treatment alternative in certain cases of chronic neuropathic pain should continue to be rigorously evaluated.

Neurophysiological evidence of antidromic activation of large myelinated fibres in lower limbs during spinal cord stimulation.

STUDY DESIGN: This study was designed to verify the hypothesis of a constant, antidromic activation of fibers traveling along peripheral sensory nerves during spinal cord stimulation (SCS). OBJECTIVE: To investigate the neurophysiological characteristics (latency, amplitude, waveform) of potentials recorded in peripheral sensory nerves during the SCS. SUMMARY OF BACKGROUND DATA: SCS is widely used for the relief of chronic benign pain resistant to conservative therapies, but its antalgic mechanism is poorly understood. Antidromic activation of peripheral nerve fibers is one of the hypothesized antalgic mechanisms, but very few neurophysiological studies have been conducted on this subject. METHODS: Sixteen patients undergoing a percutaneous test trial of SCS for chronic pain in the lower limb (4 males, 12 females, mean age of 54.2, and age range 41-77 years) were enrolled. Diagnoses included: failed back surgery syndrome, complex regional pain syndrome type I, painful lumbosacral radiculopathy, and painful peripheral neuropathy. All patients had a lead percutaneously implanted in the epidural space at a vertebral level ranging from T9-T12. Nerve action potentials were generally recorded in nonpainful leg but, when the pain was outside the investigated nerve territory, a bilateral recording was performed. Twenty-one different studies were carried out on 16 patients. RESULTS: The results confirmed the hypothesis that cutaneous afferents were regularly activated by SCS. CONCLUSION: The authors hypothesize that this antidromic activation could represent a possible antalgic mechanism of SCS in patients with peripheral neuropathic pain, but further neurophysiological studies will be needed to elucidate this hypothesis.

A case report of subcutaneous peripheral nerve stimulation for the treatment of axial back pain associated with postlaminectomy syndrome.

Objective. This article aims to present a case of the use of an alternative form of neuromodulation for the treatment of axial back pain associated with postlaminectomy syndrome. Materials and Methods. An elderly patient with long-standing axial back pain in the setting of a prior decompressive laminectomy presented for evaluation and treatment. After failing to obtain significant benefit from more conservative measures, a trial of peripheral nerve stimulation (PNS) was performed. Results. The patient reported > 75% relief of his pain during the seven-day trial period, and accordingly a permanent PNS system was implanted. The permanent system consisted of four Medtronic Quad Plus leads, two on each side of midline oriented horizontally over the L4-5 paraspinous muscles. Our patient was ultimately weaned off of all narcotic medications and, at one year follow-up, continues to report > 90% reduction of pain.

Subcutaneous peripheral nerve stimulation treatment for chronic pelvic pain.

Two cases of chronic pelvic pain of unknown etiology with symptoms referable to the low abdominal wall are presented. These patients are often difficult to manage because of multiple causes and multiple pathways for pain transmission from the pelvis. In these cases, the patients' complaints were refractory to medication management, as well as diagnostic and therapeutic nerve blockade. After careful evaluation, a successful trial of peripheral nerve stimulation was followed by permanent implantation of low abdominal subcutaneous leads and a pulse generator device. The patients reported excellent relief of their chronic pelvic pain. The use of neuromodulation via peripheral stimulation deserves further investigation as an alternative to spinal cord stimulation for chronic pelvic pain.