Factors Predicting Clinically Relevant Pain Relief After Spinal Cord Stimulation for Patients With Chronic Low Back and/or Leg Pain: A Systematic Review With Meta-Analysis and Meta-Regression.

RATIONALE: To optimize results with spinal cord stimulation (SCS) for chronic low back pain (CLBP) and/or leg pain, including persistent spinal pain syndrome (PSPS), careful patient selection based on proved predictive factors is essential. Unfortunately, the necessary selection process required to optimize outcomes of SCS remains challenging. OBJECTIVE: This review aimed to evaluate predictive factors of clinically relevant pain relief after SCS for patients with CLBP and/or radicular leg pain, including PSPS. MATERIALS AND METHODS: In August 2023, PubMed, Cinahl, Cochrane, and EMBASE were searched to identify studies published between January 2010 and August 2023. Studies reporting the percentage of patients with ≥50% pain relief after SCS in patients with CLBP and leg pain, including PSPS at 12 or 24 months, were included. Meta-analysis was conducted to pool results for back, leg, and general pain relief. Predictive factors for pain relief after 12 months were examined using univariable and multivariable meta-regression. RESULTS: A total of 27 studies (2220 patients) were included for further analysis. The mean percentages of patients with substantial pain relief were 68% for leg pain, 63% for back pain, and 73% for general pain at 12 months follow-up, and 63% for leg pain, 59% for back pain, and 71% for general pain at 24 months follow-up assessment. The implantation method and baseline Oswestry Disability Index made the multivariable meta-regression model for ≥50% back pain relief. Sex and pain duration made the final model for ≥50% leg pain relief. Variable stimulation and implantation method made the final model for general pain relief. CONCLUSIONS: This review supports SCS as an effective pain-relieving treatment for CLBP and/or leg pain, and models were developed to predict substantial back and leg pain relief. To provide high-grade evidence for predictive factors, SCS studies of high quality are needed in which standardized factors predictive of SCS success, based on in-patient improvements, are monitored and reported.

The Polyanalgesic Consensus Conference (PACC)®: Updates on Clinical Pharmacology and Comorbidity Management in Intrathecal Drug Delivery for Cancer Pain.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise with international representation to establish evidence-based guidance on using intrathecal drug delivery in chronic pain treatment. This Polyanalgesic Consensus Conference (PACC)® project's scope is to provide evidence-based guidance for clinical pharmacology and best practices for intrathecal drug delivery for cancer pain. 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 using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Meeting Abstracts, and Scopus from 2017 (when the 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 were based on the strength of evidence, and when evidence was scant, recommendations were based on expert consensus. RESULTS: The PACC evaluated the published literature and established evidence- and consensus-based expert opinion recommendations to guide best practices in treating cancer pain. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The PACC recommends best practices regarding the use of intrathecal drug delivery in cancer pain, with an emphasis on managing the unique disease and patient characteristics encountered in oncology. These evidence- and consensus-based expert opinion recommendations should be used as a guide to assist decision-making when clinically appropriate.

Maximal Analgesic Effect Attained by the Use of Objective Neurophysiological Measurements With Closed-Loop Spinal Cord Stimulation.

OBJECTIVES: Spinal cord stimulation (SCS) has been challenged by the lack of neurophysiologic data to guide therapy optimization. Current SCS programming by trial-and-error results in suboptimal and variable therapeutic effects. A novel system with a physiologic closed-loop feedback mechanism using evoked-compound action potentials enables the optimization of physiologic neural dose by consistently and accurately activating spinal cord fibers. We aimed to identify neurophysiologic dose metrics and their ranges that resulted in clinically meaningful treatment responses. MATERIALS AND METHODS: Subjects from 3 clinical studies (n = 180) with baseline back and leg pain ≥60 mm visual analog scale and physical function in the severe to crippled category were included. Maximal analgesic effect (MAE) was operationally defined as the greatest percent reduction in pain intensity or as the greatest cumulative responder score (minimal clinically important differences [MCIDs]) obtained within the first 3 months of SCS implant. The physiologic metrics that produced the MAE were analyzed. RESULTS: We showed that a neural dose regimen with a high neural dose accuracy of 2.8µV and dose ratio of 1.4 resulted in a profound clinical benefit to chronic pain patients (MAE of 79 ± 1% for pain reduction and 12.5 ± 0.4 MCIDs). No differences were observed for MAE or neurophysiological dose metrics between the trial phase and post-implant MAE visit. CONCLUSION: For the first time, an evidence-based neural dose regimen is available for a neurostimulation intervention as a starting point to enable optimization of clinical benefit, monitoring of adherence, and management of the therapy.

6. Persistent spinal pain syndrome type 2.

INTRODUCTION: Persistent Spinal Pain Syndrome (PSPS) refers to chronic axial pain and/or extremity pain. Two subtypes have been defined: PSPS-type 1 is chronic pain without previous spinal surgery and PSPS-type 2 is chronic pain, persisting after spine surgery, and is formerly known as Failed Back Surgery Syndrome (FBSS) or post-laminectomy syndrome. The etiology of PSPS-type 2 can be gleaned using elements from the patient history, physical examination, and additional medical imaging. Origins of persistent pain following spinal surgery may be categorized into an inappropriate procedure (eg a lumbar fusion at an incorrect level or for sacroiliac joint [SIJ] pain); technical failure (eg operation at non-affected levels, retained disk fragment, pseudoarthrosis), biomechanical sequelae of surgery (eg adjacent segment disease or SIJ pain after a fusion to the sacrum, muscle wasting, spinal instability); and complications (eg battered root syndrome, excessive epidural fibrosis, and arachnoiditis), or undetermined. METHODS: The literature on the diagnosis and treatment of PSPS-type 2 was retrieved and summarized. RESULTS: There is low-quality evidence for the efficacy of conservative treatments including exercise, rehabilitation, manipulation, and behavioral therapy, and very limited evidence for the pharmacological treatment of PSPS-type 2. Interventional treatments such as pulsed radiofrequency (PRF) of the dorsal root ganglia, epidural adhesiolysis, and spinal endoscopy (epiduroscopy) might be beneficial in patients with PSPS-type 2. Spinal cord stimulation (SCS) has been shown to be an effective treatment for chronic, intractable neuropathic limb pain, and possibly well-selected candidates with axial pain. CONCLUSIONS: The diagnosis of PSPS-type 2 is based on patient history, clinical examination, and medical imaging. Low-quality evidence exists for conservative interventions. Pulsed radiofrequency, adhesiolysis and SCS have a higher level of evidence with a high safety margin and should be considered as interventional treatment options when conservative treatment fails.

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.

Association Between Levels of Functional Disability and Health-Related Quality of Life With Spinal Cord Stimulation for Chronic Pain.

OBJECTIVES: Pain score, functional disability, and health-related quality of life (HRQoL) are core outcome domains for chronic pain clinical trials. Although greater levels of pain reduction have been shown to be linked to larger gains in HRQoL, little is known of the association between HRQoL and disability in the setting of chronic pain. The aims of this study were to 1) investigate the association between functional disability and HRQoL and 2) estimate the utility values associated with levels of functional disability in patients treated with evoked compound action potential (ECAP) spinal cord stimulation (SCS) for chronic pain. MATERIALS AND METHODS: Data on functional disability assessed using the Oswestry Disability Index (ODI) and HRQoL (EQ-5D-5L) were collected from 204 patients with an Evoke ECAP-SCS device and followed up to 12 months. SF-6D utility scores also were retrieved for 134 of these patients. Multivariable linear regression models adjusted for baseline utility values and patient demographics were used to compare differences in utility values across ODI categories. RESULTS: Significant improvements in functional disability and HRQoL were observed at three- and 12-month follow-up after SCS. Patients reporting "minimum disability," "moderate disability," "severe disability," and "crippled" had mean EQ-5D scores of 0.82, 0.73, 0.59, and 0.45, respectively. The mean change in EQ-5D score was 0.007 per unit change in total ODI score. The R2 statistic showed a moderate level association (49%-64% of variance in EQ-5D explained by ODI). CONCLUSION: ECAP-SCS results in significant improvements in functional disability and HRQoL. This study shows that improvement in function of people with chronic pain before and after ECAP-SCS is associated with improvement in HRQoL.

Early Experience With a Novel Miniaturized Spinal Cord Stimulation System for the Management of Chronic Intractable Pain of the Back and Legs.

INTRODUCTION: A novel, spinal cord stimulation (SCS) system with a battery-free miniaturized implantable pulse generator (IPG) was used in this feasibility study. The system uses an external power source that communicates bidirectionally with the IPG (< 1.5 cm3). Human factors, subject comfort, and effects on low back and leg pain were evaluated in this first-in-human study. MATERIALS AND METHODS: A prospective, multicenter, open-label clinical trial was initiated to evaluate the safety and performance of a novel miniaturized stimulator in the treatment of chronic, intractable leg and low-back pain. Eligible subjects were recruited for the study and gave consent. Subjects who passed the screening/trial phase (defined as ≥ 50% decrease in pain) continued to the long-term implant phase and were followed up at predefined time points after device activation. Interim clinical and usability outcomes were captured and reported at 90 days. RESULTS: Results of 22 subjects who chose a novel pulsed stimulation pattern therapy using the battery-free IPG (< 1.5 cm3) are described here. At 90-days follow-up, the average pain reduction was 79% in the leg (n = 22; p < 0.0001) and 76% in the low back (n = 21; p < 0.0001) compared with baseline. Responder rates (≥ 50% pain relief) at 90 days were 86% in leg pain (19/22) and 81% in low-back pain (17/21). Subjects rated the level of comfort of the external wearable power source to be 0.41 ± 0.73 at 90 days on an 11-point rating scale (0 = very comfortable, 10 = very uncomfortable). DISCUSSION: These interim results from the ongoing study indicate the favorable efficacy and usability of a novel, externally powered, battery-free SCS IPG (< 1.5 cm3) for leg and low-back pain. Study subjects wore the external power source continuously and found it comfortable, and the system provided significant pain relief. These preliminary findings warrant further investigation. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is ACTRN12618001862235.

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.

A Novel Pulsed Stimulation Pattern in Spinal Cord Stimulation: Clinical Results and Postulated Mechanisms of Action in the Treatment of Chronic Low Back and Leg Pain.

OBJECTIVES: The aim of this article is to discuss the possible mechanisms of action (MOAs) and results of a pilot study of a novel, anatomically placed, and paresthesia-independent, neurostimulation waveform for the management of chronic intractable pain. MATERIALS AND METHODS: A novel, multilayered pulsed stimulation pattern (PSP) that comprises three temporal layers, a Pulse Pattern layer, Train layer, and Dosage layer, was developed for the treatment of chronic intractable pain. During preliminary development, the utility was evaluated of anatomical PSP (aPSP) in human subjects with chronic intractable pain of the leg(s) and/or low back, compared with that of traditional spinal cord stimulation (T-SCS) and physiological PSP. The scientific theory and testing presented in this article provide the preliminary justification for the potential MOAs by which PSP may operate. RESULTS: During the pilot study, aPSP (n = 31) yielded a greater decrease in both back and leg pain than did T-SCS (back: -60% vs -46%; legs: -63% vs -43%). In addition, aPSP yielded higher responder rates for both back and leg pain than did T-SCS (61% vs 48% and 78% vs 50%, respectively). DISCUSSION: The novel, multilayered approach of PSP may provide multimechanistic therapeutic relief through preferential fiber activation in the dorsal column, optimization of the neural onset response, and use of both the medial and lateral pathway through the thalamic nuclei. The results of the pilot study presented here suggest a robust responder rate, with several subjects (five subjects with back pain and three subjects with leg pain) achieving complete relief from PSP during the acute follow-up period. These clinical findings suggest PSP may provide a multimechanistic, anatomical, and clinically effective management for intractable chronic pain. Because of the limited sample size of clinical data, further testing and long-term clinical assessments are warranted to confirm these preliminary 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.

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.

Ten kHz spinal cord stimulation for the treatment of chronic peripheral polyneuropathy: 12-Month results from prospective open-label pilot study.

BACKGROUND: The goal of this study was to demonstrate that the paresthesia-independent 10 kHz spinal cord stimulation (SCS) can provide long-term pain relief in patients with peripheral polyneuropathy (PPN). Clinically diagnosed subjects with PPN refractory to conventional medical management were enrolled in this prospective, multicenter study between November 2015 and August 2016, after institutional review board approval and patient informed consent were obtained. METHODS: Subjects underwent trial stimulation utilizing 2 epidural leads, and if successful, were implanted with a permanent 10 kHz SCS system and followed up for 12 months post-implant. Outcome measures included adverse events, pain, neurological assessments, disability, function, quality of life, pain interference, sleep, satisfaction, and global impression of change. Data are presented as descriptive statistics. Permanent implant population results are reported as mean ± standard error. RESULTS: Twenty-one of the 26 trialed subjects had a successful trial and 18 received a permanent implant. All subjects had the leads placed anatomically without the need for paresthesia. Subjects experienced significant and sustained pain relief (at least 65% at all timepoints) whereas physicians noted improvements in neurological function. Significant improvements in disability, function, sleep, sensory, and affective dimensions of pain were reported at all timepoints. All adverse events were resolved without sequelae. CONCLUSION: Findings from this study suggest that 10 kHz SCS may provide sustained pain relief and disability improvements in patients suffering from PPN.

The Use of Non-invasive Vagus Nerve Stimulation to Treat Respiratory Symptoms Associated With COVID-19: A Theoretical Hypothesis and Early Clinical Experience.

OBJECTIVES: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a pandemic with no specific therapeutic agents and substantial mortality, and finding new treatments is critical. Most cases are mild, but a significant minority of patients develop moderate to severe respiratory symptoms, with the most severe cases requiring intensive care and/or ventilator support. This respiratory compromise appears to be due to a hyperimmune reaction, often called a cytokine storm. Vagus nerve stimulation has been demonstrated to block production of cytokines in sepsis and other medical conditions. We hypothesize that non-invasive vagus nerve stimulation (nVNS) might provide clinical benefits in patients with respiratory symptoms similar to those associated with COVID-19. MATERIALS AND METHODS: Information on two case reports was obtained via email correspondence and phone interviews with the patients. RESULTS: Both patients reported clinically meaningful benefits from nVNS therapy. In case 1, the patient used nVNS to expedite symptomatic recovery at home after hospital discharge and was able to discontinue use of opioid and cough suppressant medications. In case 2, the patient experienced immediate and consistent relief from symptoms of chest tightness and shortness of breath, as well as an improved ability to clear his lungs. CONCLUSIONS: Preliminary observations and a strong scientific foundation suggest that nVNS might provide clinical benefits in patients with COVID-19 via multiple mechanisms.

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.

Vagus nerve stimulation for primary headache disorders: An anatomical review to explain a clinical phenomenon.

BACKGROUND: Non-invasive stimulation of the vagus nerve has been proposed as a new neuromodulation therapy to treat primary headache disorders, as the vagus nerve is hypothesized to modulate the headache pain pathways in the brain. Vagus nerve stimulation can be performed by placing an electrode on the ear to stimulate the tragus nerve, which contains about 1% of the vagus fibers. Non-invasive vagus nerve stimulation (nVNS) conventionally refers to stimulation of the cervical branch of the vagus nerve, which is made up entirely of vagal nerve fibers. While used interchangeably, most of the research to date has been performed with nVNS or an implanted vagus nerve stimulation device. However, the exact mechanism of action of nVNS remains hypothetical and no clear overview of the effectiveness of nVNS in primary headache disorders is available. METHODS: In the present study, the clinical trials that investigated the effectiveness, tolerability and safety of nVNS in primary headache disorders were systematically reviewed. The second part of this study reviewed the central connections of the vagus nerve. Papers on the clinical use of nVNS and the anatomical investigations were included based on predefined criteria, evaluated, and results were reported in a narrative way. RESULTS: The first part of this review shows that nVNS in primary headache disorders is moderately effective, safe and well-tolerated. Regarding the anatomical review, it was reported that fibers from the vagus nerve intertwine with fibers from the trigeminal, facial, glossopharyngeal and hypoglossal nerves, mostly in the trigeminal spinal tract. Second, the four nuclei of the vagus nerve (nuclei of the solitary tract, nucleus ambiguus, spinal nucleus of the trigeminal nerve and dorsal motor nucleus (DMX)) show extensive interconnections. Third, the efferents from the vagal nuclei that receive sensory and visceral input (i.e. nuclei of the solitary tract and spinal nucleus of the trigeminal nerve) mainly course towards the main parts of the neural pain matrix directly or indirectly via other vagal nuclei. CONCLUSION: The moderate effectiveness of nVNS in treating primary headache disorders can possibly be linked to the connections between the trigeminal and vagal systems as described in animals.

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.

Success Using Neuromodulation With BURST (SUNBURST) Study: Results From a Prospective, Randomized Controlled Trial Using a Novel Burst Waveform.

OBJECTIVE: The purpose of the multicenter, randomized, unblinded, crossover Success Using Neuromodulation with BURST (SUNBURST) study was to determine the safety and efficacy of a device delivering both traditional tonic stimulation and burst stimulation to patients with chronic pain of the trunk and/or limbs. METHODS: Following a successful tonic trial, 100 subjects were randomized to receive one stimulation mode for the first 12 weeks, and then the other stimulation mode for the next 12 weeks. The primary endpoint assessed the noninferiority of the within-subject difference between tonic and burst for the mean daily overall VAS score. An intention-to-treat analysis was conducted using data at the 12- and 24-week visits. Subjects then used the stimulation mode of their choice and were followed for one year. Descriptive statistics were used analyze additional endpoints and to characterize the safety profile of the device. RESULTS: The SUNBURST study demonstrated that burst stimulation is noninferior to tonic stimulation (p < 0.001). Superiority of burst was also achieved (p < 0.017). Significantly more subjects (70.8%) preferred burst stimulation over tonic stimulation (p < 0.001). Preference was sustained through one year: 68.2% of subjects preferred burst stimulation, 23.9% of subjects preferred tonic, and 8.0% of subjects had no preference. No unanticipated adverse events were reported and the safety profile was similar to other spinal cord stimulation studies. CONCLUSIONS: The SUNBURST study demonstrated that burst spinal cord stimulation is safe and effective. Burst stimulation was not only noninferior but also superior to tonic stimulation for the treatment of chronic pain. A multimodal stimulation device has advantages.

The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines.

INTRODUCTION: Pain treatment is best performed when a patient-centric, safety-based philosophy is used to determine an algorithmic process to guide care. Since 2007, the International Neuromodulation Society has organized a group of experts to evaluate evidence and create a Polyanalgesic Consensus Conference (PACC) to guide practice. METHODS: The current PACC update was designed to address the deficiencies and innovations emerging since the previous PACC publication of 2012. An extensive literature search identified publications between January 15, 2007 and November 22, 2015 and authors contributed additional relevant sources. After reviewing the literature, the panel convened to determine evidence levels and degrees of recommendations for intrathecal therapy. This meeting served as the basis for consensus development, which was ranked as strong, moderate or weak. Algorithms were developed for intrathecal medication choices to treat nociceptive and neuropathic pain for patients with cancer, terminal illness, and noncancer pain, with either localized or diffuse pain. RESULTS: The PACC has developed an algorithmic process for several aspects of intrathecal drug delivery to promote safe and efficacious evidence-based care. Consensus opinion, based on expertise, was used to fill gaps in evidence. Thirty-one consensus points emerged from the panel considerations. CONCLUSION: New algorithms and guidance have been established to improve care with the use of intrathecal drug delivery.