Restorative neurostimulation for chronic mechanical low back pain - Three year results from the United Kingdom post market clinical follow-up registry.

Introduction: Mechanical chronic low back pain is often associated with impaired neuromuscular control of the lumbar multifidus muscles, the most important stabilizers of the lumbar spine. Restorative neurostimulation is a modality for the treatment for this specific subset of patients aimed to facilitate restoration of neuromuscular control by bilateral stimulation of the L2 medial branches. Evidence from both prospective and randomised clinical trials to date has demonstrated substantial improvements in clinical outcomes such as pain, disability and health-related quality of life. Methods: This study is an open label prospective follow-up for the treatment of chronic mechanical low back pain of nociceptive origin with restorative neurostimulation. Patients completed assessments for pain, disability and health-related quality of life. Outcomes were collected at 45, 90 and 180 days, and 1, 2 and 3 years after the activation visit. Results: Forty-two patients were implanted with the device and 33 (79%) were available at the 3-year appointment. Patients in this cohort presented with severe chronic low back pain (NRS = 7.0 ± 0.2) and severe disability (ODI 46.6 ± 12.0). The health-related quality of life was also severely impacted at baseline (EQ-5D 0.426 ± 0.061). Changes in pain, disability and quality of life at three-year follow-up demonstrated a statistically significant improvement between baseline and 1, 2 and 3 years. After 3 years of therapy, average NRS scores had reduced to 2.7± 0.3 and mean ODI score to 26.0 ± 3.1 while EQ-5D-5L index improved to 0.707 ± 0.036. Conclusions: The ongoing follow-up of this post market cohort continues to demonstrate that restorative neurostimulation provides a statistically significant, clinically meaningful and durable response across pain, disability and quality-of life scores for patients suffering chronic mechanical low back pain that has been refractory to conventional management. Trial Registration: ClinicalTrials.gov Identifier: NCT01985230.

Long-term safety of spinal cord stimulation systems in a prospective, global registry of patients with chronic pain.

Aim: The availability of long-term (>2 years) safety outcomes of spinal cord stimulation (SCS) remains limited. We evaluated safety in a global SCS registry for chronic pain. Methods: Participants were prospectively enrolled globally at 79 implanting centers and followed out to 3 years after device implantation. Results: Of 1881 participants enrolled, 1289 received a permanent SCS implant (1776 completed trial). The annualized rate of device explant was 3.5% (all causes), and 1.1% due to inadequate pain relief. Total incidence of device explantation >3 years was 7.6% (n = 98). Of these, 32 subjects (2.5%) indicated inadequate pain relief as cause for removal. Implant site infection (11 events) was the most common device-related serious adverse event (<1%). Conclusion: This prospective, global, real-world study demonstrates a high-level of safety for SCS with low rate of explant/serious adverse events. Clinical Trial Registration: NCT01719055 (ClinicalTrials.gov).

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.

Real-World Outcomes Using a Spinal Cord Stimulation Device Capable of Combination Therapy for Chronic Pain: A European, Multicenter Experience.

Given the differing mechanisms thought to underlie therapeutic sub- and supra-perception-based neurostimulative modalities, Spinal Cord Stimulation (SCS) systems designed for combined delivery of these approaches may help improve analgesic outcomes and quality of life, and reduce treatment failures. This multicenter, observational case-series evaluated 188 patients with chronic back and/or leg pain implanted with an SCS device capable of sequential or simultaneous delivery of sub-perception and supra-perception stimulation programming (i.e., combination therapy) at 16 in Europe. Following implantation, patients were provided with an array of advanced supra-perception programs (e.g., paresthesia-based SCS using multiple independent current sources), and a custom set of sub-perception programs optimized with specific waveforms and/or field shapes. A mean overall pain score of 7.9 ± 1.7 (Standard Deviation (SD)) was reported pre-trial (Baseline). Overall pain was reduced by 4.4 ± 2.8 points (NRS) at 3-months (n = 117) and at 12 months post-implant (n = 90), respectively (p < 0.0001). Substantial quality-of-life (EQ-5D-5L) improvement as assessed at last follow-up was also observed (n = 60). These results suggest that an implanted SCS device capable of combination therapy, while also enabled with patient-specific waveform optimization and stimulation field targeting capabilities, can enable highly effective pain relief and improve quality of life in patients suffering with chronic pain.

Restorative Neurostimulation for Chronic Mechanical Low Back Pain: Results from a Prospective Multi-centre Longitudinal Cohort.

INTRODUCTION: Low back pain impacts most people throughout the course of their lives and contributes significantly to the global burden of disease. In some patients, symptoms resolve with little intervention, while others are amenable to surgical intervention, some cases are intractable to current care paradigms. Restorative neurostimulation is an emerging therapy for chronic mechanical low back pain. METHODS: We conducted a prospective post-market follow-up of 42 patients treated for longstanding chronic mechanical low back pain with restorative neurostimulation. Patients were followed up at 45, 90, and 180 days and 1 and 2 years following activation of the device. Pain, disability, and health-related quality of life were recorded. RESULTS: Among the 37 patients completing 2-year follow-up, numerical rating scale (NRS) pain scores improved from 7.0 ± 0.2 to 3.5 ± 0.3 (p < 0.001), Oswestry Disability Index (ODI) scores improved from 46.2 ± 2.2 to 29.2 ± 3.1 (p < 0.001), and health-related quality of life (measured by the EuroQol 5-Dimension 5-Level questionnaire-EQ-5D-5L) improved from 0.426 ± 0.035 to 0.675 ± 0.030 (p < 0.001). Additionally, 57% of patients experienced a greater than 50% reduction in pain, and 51% of patients benefited by a greater than 15-point reduction in ODI, both substantial improvements. CONCLUSION: This real-world sample of patients shows that restorative neurostimulation can provide substantial and durable benefit to a cohort of patients that have traditionally had few reliable treatment options. Our findings support the continued used of this therapy in well-selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01985230.

The goal of this study was to examine the effectiveness of restorative neurostimulation for the treatment of patients with chronic mechanical low back pain. This technique has been studied in a clinical trial setting and been shown to be both safe and effective. This study reports on the real-world experience from five sites in the United Kingdom. Patients with a history of severe low back pain that lasted on average for more than 13 years were implanted with a nerve stimulation device that targets the nerves that control important spinal stabilising muscles. All of the patients were asked to perform two stimulation sessions per day for 30 min each. Over the next 2 years, patients reported substantial reductions in pain and disability and an improvement in health-related quality of life. The safety profile of the therapy was excellent when compared to similar minimally invasive therapies for different spine pathologies. In this difficult-to-treat patient population who have few remaining therapeutic options, restorative neurostimulation is a valuable tool in the clinician's armamentarium.

Seeing White: Management of TIVA during autologous breast reconstruction.

Total IntraVenous Anaesthesia is frequently the anaesthetic of choice for enhanced recovery after surgery pathways during breast reconstruction free flap surgery. This relies upon the continuous intravenous infusion of propofol. We describe our experience of two patients where augmentation of a venously congested DIEP flap with a cephalic vein transposition procedure, risked interruption of the intravenous delivery of anaesthesia to the patient. We also share our steps taken to mitigate this risk going forward.

Neuromodulation.

Spinal cord stimulation is the main neuromodulation therapy for certain chronic neuropathic pain conditions. This article describes neuromodulation and the process of spinal cord stimulation therapy. It also clarifies the suitability of a patient for referral and consideration for spinal cord stimulation.

Multicentre, clinical trial of burst spinal cord stimulation for neck and upper limb pain NU-BURST: a trial protocol.

BACKGROUND: Spinal cord stimulation (SCS) is an established therapy for chronic neuropathic pain and most frequently utilised for Failed Back Surgery Syndrome (FBSS). BurstDR™ also known as DeRidder Burst-SCS, a novel waveform, has demonstrated superiority to conventional tonic stimulation of the thoracic spine in FBSS. There are case reports of an improvement in multidimensional pain outcomes using DeRidder Burst-SCS in the cervical spine for chronic neck and cervical radicular pain. The safety and efficacy of cervical DeRidder Burst-SCS stimulation still however remain undetermined. METHODS/DESIGN: This is a prospective, multicentre feasibility trial evaluating the safety and therapeutic efficacy of DeRidder Burst-SCS stimulation for the treatment of chronic intractable neck pain with or without radiation to the arm, shoulder, and upper back. After baseline evaluation, subjects will undergo an SCS trial using the Abbott Invisible Trial system according to standard clinical procedures. During the trial phase, SCS leads will be implanted in the cervical epidural space. At the end of the SCS trial, subjects experiencing at least 50% pain relief will be considered for permanent implant. Pain intensity, medication usage, and other multidimensional pain outcomes will be collected. The timing of these will be at baseline, end of the SCS trial and at 3-, 6-, and 12-month visits. Incidence of adverse events will be collected throughout the study duration. DISCUSSION: The results of this feasibility study will validate the efficacy and safety of DeRidder Burst-SCS stimulation in the cervical spine. The results obtained in this study will potentially be used to generate a level 1 evidence-based study with formal statistical hypotheses testing. TRIAL REGISTRATION: www.clinicaltrials.gov Identifier: NCT03159169.

Effects of Rate on Analgesia in Kilohertz Frequency Spinal Cord Stimulation: Results of the PROCO Randomized Controlled Trial.

OBJECTIVE: The PROCO RCT is a multicenter, double-blind, crossover, randomized controlled trial (RCT) that investigated the effects of rate on analgesia in kilohertz frequency (1-10 kHz) spinal cord stimulation (SCS). MATERIALS AND METHODS: Patients were implanted with SCS systems and underwent an eight-week search to identify the best location ("sweet spot") of stimulation at 10 kHz within the searched region (T8-T11). An electronic diary (e-diary) prompted patients for pain scores three times per day. Patients who responded to 10 kHz per e-diary numeric rating scale (ED-NRS) pain scores proceeded to double-blind rate randomization. Patients received 1, 4, 7, and 10 kHz SCS at the same sweet spot found for 10 kHz in randomized order (four weeks at each frequency). For each frequency, pulse width and amplitude were titrated to optimize therapy. RESULTS: All frequencies provided equivalent pain relief as measured by ED-NRS (p ≤ 0.002). However, mean charge per second differed across frequencies, with 1 kHz SCS requiring 60-70% less charge than higher frequencies (p ≤ 0.0002). CONCLUSIONS: The PROCO RCT provides Level I evidence for equivalent pain relief from 1 to 10 kHz with appropriate titration of pulse width and amplitude. 1 kHz required significantly less charge than higher frequencies.

Deep brain stimulation of the periaqueductal gray releases endogenous opioids in humans.

Deep brain stimulation (DBS) of the periaqueductal gray (PAG) is used in the treatment of severe refractory neuropathic pain. We tested the hypothesis that DBS releases endogenous opioids to exert its analgesic effect using [11C]diprenorphine (DPN) positron emission tomography (PET). Patients with de-afferentation pain (phantom limb pain or Anaesthesia Dolorosa (n=5)) who obtained long-lasting analgesic benefit from DBS were recruited. [11C]DPN and [15O]water PET scanning was performed in consecutive sessions; first without, and then with PAG stimulation. The regional cerebral tracer distribution and kinetics were quantified for the whole brain and brainstem. Analysis was performed on a voxel-wise basis using statistical parametric mapping (SPM) and also within brainstem regions of interest and correlated to the DBS-induced improvement in pain score and mood. Brain-wide analysis identified a single cluster of reduced [11C]DPN binding (15.5% reduction) in the caudal, dorsal PAG following DBS from effective electrodes located in rostral dorsal/lateral PAG. There was no evidence for an accompanying focal change in blood flow within the PAG. No correlation was found between the change in PAG [11C]DPN binding and the analgesic effect or the effect on mood (POMSSV) of DBS. The analgesic effect of DBS in these subjects was not altered by systemic administration of the opioid antagonist naloxone (400ug). These findings indicate that DBS of the PAG does indeed release endogenous opioid peptides focally within the midbrain of these neuropathic pain patients but we are unable to further resolve the question of whether this release is responsible for the observed analgesic benefit.

Novel use of narrow paddle electrodes for occipital nerve stimulation--technical note.

OBJECTIVES: Occipital nerve stimulation (ONS), an established treatment for medically intractable headache syndromes, has lead migration rates quoted up to 24%. In a series of patients with ideal characteristics for this treatment modality, we describe an operative technique for ONS involving the novel use of narrow paddle electrodes: "S8 Lamitrode" (St. Jude Medical [SJM], St. Paul, MN, USA). MATERIALS AND METHODS: Five patients (occipital neuralgia [ON] = 4; chronic migraine [CM] = 1) were treated with ONS between 2010 and 2011. All patients had a successful trial of peripheral neurostimulation (Algotec Ltd, Crawley, UK) therapy. Operative technique involved the use of a park-bench position, allowing simultaneous exposure of the occipital and infraclavicular regions. Through a retromastoid/occipital incision just beneath the external occipital protruberance, exposing the extrafascial plane, the S8 Lamitrode is implanted to intersect both greater occipital nerves for bilateral pain or unilateral greater and lesser occipital nerves for unilateral ON or with significant component of the pain relating to the lesser occipital nerve. RESULTS: Over the median follow-up of 12 months, there were no episodes of lead migration or revision. There also was significant improvement in symptoms in all patients. CONCLUSIONS: This is the first reported use of S8 Lamitrode electrode for ONS. This narrow electrode is suited for this role leading to minimal trauma during surgical placement, facilitates resolution of problems with lead migration, and optimizes effect with stimulation focused more in direction of the occipital nerves without skin involvement. To date, the SJM Genesis neurostimulation system, with percutaneous electrodes only, is CE mark approved in Europe for peripheral nerve stimulation of the occipital nerves for the management of pain and disability for patients diagnosed with intractable CM. Further developments and studies are required for better devices to suit ONS, thereby avoiding frequently encountered problems and which may clarify the role of paddle leads in ONS.

Analgesia in conjunction with normalisation of thermal sensation following deep brain stimulation for central post-stroke pain.

The aetiology of central post-stroke pain (CPSP) is poorly understood and such pains are often refractory to treatment. We report the case of a 56-year-old man, who, following a temporo-parietal infarct, suffered from debilitating and refractory hemi-body cold dysaesthesia and severe tactile allodynia. This was associated with thermal and tactile hypoaesthesia and hypoalgesia on his affected side. Implantation of a deep brain stimulating electrode in his periventricular gray (PVG) region produced an improvement in his pain that was associated with a striking normalisation of his deficits in somatosensory perception. This improvement in pain and thermal sensibility was reversed as stimulation became less effective, because of increased electrode impedance. Therefore, we postulate that the analgesic benefit may have occurred as a consequence of the normalisation of somatosensory function and we discuss these findings in relation to the theories of central pain generation and the potential to engage useful plasticity in central circuits.

Homotopic stimulation can reduce the area of allodynia in patients with neuropathic pain.

Allodynia is a common, troublesome feature of neuropathic pain conditions. In a previous study of postherpetic neuralgia we observed that repeated tactile stimulation appeared to reduce the size of the area of allodynia in some patients. We have undertaken a pragmatic clinical study to characterise this phenomenon in neuropathic pain patients with a range of different aetiologies. Neuropathic pain patients with a discrete area of tactile allodynia were recruited (n=20). We assessed the sensitive area using punctate and dynamic tactile stimuli, and thermal quantitative sensory testing. On two separate testing visits, the patients had repeated (10x over 1 min) noxious heat or cotton bud strokes applied to the affected site or contralaterally. Tactile stimulation of the affected area evoked pain (median 7 NRS) and a reduction (>30%) in the area of allodynia in 9/18 patients (maximum -48+/-9%, after 20 min), although the intensity of allodynic pain was unchanged. This effect persisted for over 1h and was present the following day in all patients tested (n=5/5). No subjects showed an increase in area after allodynic stimulation. There was no change in heat pain threshold at a distant site following allodynic stimulation, suggesting no activation of diffuse noxious inhibitory control. Repeated thermal noxious stimulation (median NRS 7) could also elicit changes (>30%) in the area of allodynia in some patients (reductions in 7/20, increases in 3/20). Thus, we have found that a brief period of homotopic painful stimulation can reduce the area of allodynia in around half of patients with established neuropathic pains.