Levy, Robert M.

Background The efficacy of EVOKE therapy, a closed-loop spinal cord stimulation (SCS) system, has been demonstrated in a double-blinded randomized controlled trial (RCT). RCT evidence, however, may not be generalizable to clinical practice, while limitations of real-world evidence may affect its validity. The aim of this study was to evaluate the effectiveness of EVOKE therapy in routine clinical practice employing a rigorous data collection approach. Methods The ECAP study was a prospective, multicenter, single-arm, pragmatic study that enrolled SCS candidates with chronic, intractable trunk and/or limb pain in 22 US investigational sites. PROMIS-29 questionnaire and objective neurophysiological metrics were collected, and minimal clinically important differences (MCIDs) were used to characterize baseline dysfunction and response to EVOKE therapy both at trial end and maximal analgesic effect post-implant visit. Pre-specified subgroup analyses were conducted based on diagnosis. Results EVOKE therapy observed included a dose ratio of 1.3 and neural dose accuracy of 2.8 μV. Improvements of >1 MCID were observed for all domains and improvements of ≥2 MCIDs were observed for six of the seven domains. Improvements observed at trial end were maintained or improved at post-implant visit, with statistically significant improvement in holistic MCID (MD 0.2, 95% CI 0.1 to 0.4, p=0.004), and a significantly greater proportion of patients considered holistic MCID responders (p=0.047). Subgroup analysis by diagnosis showed similar outcomes. Conclusions EVOKE therapy was associated with clinically meaningful improvements in a real-world chronic pain population across different subgroups and disease pathologies, with effects observed at trial end reproduced at post-implant visit.

Abstract Introduction DISTINCT is a randomized controlled trial evaluating passive recharge burst SCS compared with CMM in improving pain and pain‐related physical function in patients suffering from chronic back pain without prior lumbar surgery, and for whom corrective surgery is not an option. Sub‐analyses of outcome measures are presented for a subset implanted with paddle leads at both 6 and 12 months. Objective To investigate the treatment effect of using BurstDR‐capable SCS in nonsurgical low back pain (NSLBP) patients with paddle leads. Methods An independent board‐certified spine surgeon reviewed each case, confirming a lack of corrective surgical options. Out of 29 sites and 115 implants, 10 sites implanted 50 patients with paddle leads. Primary and secondary endpoints assessed improvements in low back pain intensity (NRS), low back pain‐related disability (ODI), pain catastrophizing (PCS), and patient global impression of change (PGIC). Results Data for patients with NSLBP and implanted with paddle leads are available for 47 and 44 patients at 6 and 12 months, respectively. Patients reported significant reductions in pain relief at 6 and 12 months, decreasing from 7.8 ± 1.2 at baseline to 2.0 ± 1.6 and 2.2 ± 2.2, respectively ( p < 0.0001). Disability was substantially reduced (> 20 points) from severe to mild at 6 and 12 months; ODI reduced from 54.4 ± 15.0 at baseline to 19.9 ± 14.1 and 22.1 ± 13.6, respectively ( p < 0.0001). Pain catastrophizing improved to reflect the average of a non‐chronic pain population; decreased from 27.6 ± 13.1 at baseline to 8.1 ± 8.2 and 7.8 ± 9.9 ( p < 0.0001). 93.2% of patients reported a moderately better‐much‐improved outcome on PGIC. Ten complications occurred in 9 patients, 3 being severe device‐related events. Two explants were required; one due to infection and one due to persistent pain at the IPG site, and one lead‐related event was resolved by surgical repositioning. Conclusions Passive recharge burst using paddle leads provides substantial relief to patients suffering from severe, debilitating, NSLBP. Patients report significant improvements in pain, function, and pain‐related emotional distress. In addition, the rate of adverse events is low, supporting a favorable safety profile.

AbstractObjectiveTo conduct a systematic literature review of dorsal root ganglion (DRG) stimulation for pain.DesignGrade the evidence for DRG stimulation.MethodsAn international, interdisciplinary work group conducted a literature search for DRG stimulation. Abstracts were reviewed to select studies for grading. General inclusion criteria were prospective trials (randomized controlled trials and observational studies) that were not part of a larger or previously reported group. Excluded studies were retrospective, too small, or existed only as abstracts. Studies were graded using the modified Interventional Pain Management Techniques–Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria.ResultsDRG stimulation has Level II evidence (moderate) based upon one high-quality pivotal randomized controlled trial and two lower-quality studies.ConclusionsModerate-level evidence supports DRG stimulation for treating chronic focal neuropathic pain and complex regional pain syndrome.

AbstractObjectiveTo conduct a systematic literature review of peripheral nerve stimulation (PNS) for pain.DesignGrade the evidence for PNS.MethodsAn international interdisciplinary work group conducted a literature search for PNS. Abstracts were reviewed to select studies for grading. Inclusion/exclusion criteria included prospective randomized controlled trials (RCTs) with meaningful clinical outcomes that were not part of a larger or previously reported group. Excluded studies were retrospective, had less than two months of follow-up, or existed only as abstracts. Full studies were graded by two independent reviewers using the modified Interventional Pain Management Techniques–Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria.ResultsPeripheral nerve stimulation was studied in 14 RCTs for a variety of painful conditions (headache, shoulder, pelvic, back, extremity, and trunk pain). Moderate to strong evidence supported the use of PNS to treat pain.ConclusionPeripheral nerve stimulation has moderate/strong evidence. Additional prospective trials could further refine appropriate populations and pain diagnoses.

AbstractObjectiveTo conduct a systematic literature review of spinal cord stimulation (SCS) for pain.DesignGrade the evidence for SCS.MethodsAn international, interdisciplinary work group conducted literature searches, reviewed abstracts, and selected studies for grading. Inclusion/exclusion criteria included randomized controlled trials (RCTs) of patients with intractable pain of greater than one year’s duration. Full studies were graded by two independent reviewers. Excluded studies were retrospective, had small numbers of subjects, or existed only as abstracts. Studies were graded using the modified Interventional Pain Management Techniques–Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria.ResultsSCS has Level 1 evidence (strong) for axial back/lumbar radiculopathy or neuralgia (five high-quality RCTs) and complex regional pain syndrome (one high-quality RCT).ConclusionsHigh-level evidence supports SCS for treating chronic pain and complex regional pain syndrome. For patients with failed back surgery syndrome, SCS was more effective than reoperation or medical management. New stimulation waveforms and frequencies may provide a greater likelihood of pain relief compared with conventional SCS for patients with axial back pain, with or without radicular pain.

Background: Chronic migraine (CM) is a debilitating neurological disorder with few treatment options. Peripheral nerve stimulation (PNS) of the occipital nerves is a potentially promising therapy for CM patients. Methods: In this randomized, controlled multicenter study, patients diagnosed with CM were implanted with a neurostimulation device near the occipital nerves and randomized 2:1 to active ( n = 105) or sham ( n = 52) stimulation. The primary endpoint was a difference in the percentage of responders (defined as patients that achieved a ≥50% reduction in mean daily visual analog scale scores) in each group at 12 weeks. Results: There was not a significant difference in the percentage of responders in the Active compared with the Control group (95% lower confidence bound (LCB) of −0.06; p = 0.55). However, there was a significant difference in the percentage of patients that achieved a 30% reduction ( p = 0.01). Importantly, compared with sham-treated patients, there were also significant differences in reduction of number of headache days (Active Group = 6.1, baseline = 22.4; Control Group = 3.0, baseline = 20.1; p = 0.008), migraine-related disability ( p = 0.001) and direct reports of pain relief ( p = 0.001). The most common adverse event was persistent implant site pain. Conclusion: Although this study failed to meet its primary endpoint, this is the first large-scale study of PNS of the occipital nerves in CM patients that showed significant reductions in pain, headache days, and migraine-related disability. Additional controlled studies using endpoints that have recently been identified and accepted as clinically meaningful are warranted in this highly disabled patient population with a large unmet medical need. Trial registration: Clinical trials.gov (NCT00615342).