Should we Oppose or Combine Waveforms for Spinal Cord Stimulation in PSPS-T2 Patients? A Prospective Randomized Crossover Trial (MULTIWAVE Study).

Refractory persistent spinal pain syndrome after surgery (PSPS-T2) can be successfully addressed by spinal cord stimulation (SCS). While conventional stimulation generates paresthesia, recent systems enable the delivery of paresthesia-free stimulation. Studies have claimed non-inferiority/superiority of selected paresthesia-free stimulation compared with paresthesia-based stimulation, but the comparative efficacy between different waveforms still needs to be determined in a given patient. We designed a randomized controlled 3-month crossover trial to compare pain relief of paresthesia-based stimulation versus high frequency versus burst in 28 PSPS-T2 patients implanted with multiwave SCS systems. Our secondary objectives were to determine the efficacy of these 3 waveforms on pain surface, quality of life, functional capacity, psychological distress, and validated composite multidimensional clinical response index to provide holistic comparisons at 3-, 6-, 9-, and 15-month post-randomization. The preferred stimulation modality was documented during the follow-up periods. No difference between the waveforms was observed in this study (P = .08). SCS led to significant pain relief, quality of life improvement, improvement of multidimensional clinical response index, and of all other clinical outcomes at all follow-up visits. Forty-four percent of the patients chose to keep the paresthesia-based stimulation modality after the 15-month follow-up period. By giving the possibility to switch and/or to combine several waveforms, the overall rate of SCS responders further increased with 25%. In this study, high frequency or burst do not appear superior to paresthesia-based stimulation, wherefore paresthesia-based stimulation should still be considered as a valid option. However, combining paresthesia-based stimulation with paresthesia-free stimulation, through personalized multiwave therapy, might significantly improve SCS responses. PERSPECTIVE: This article assesses clinical SCS efficacy on pain relief, by comparing paresthesia-based stimulation and paresthesia-free stimulation (including high frequency and burst) modalities in patient presenting with PSPS-T2. Switching and/or combining waveforms contribute to increasing the global SCS responders rate.

Mixture of longitudinal factor analyzers and their application to the assessment of chronic pain.

Multivariate longitudinal data are used in a variety of research areas not only because they allow to analyze time trajectories of multiple indicators, but also to determine how these trajectories are influenced by other covariates. In this article, we propose a mixture of longitudinal factor analyzers. This model could be used to extract latent factors representing multiple longitudinal noisy indicators in heterogeneous longitudinal data and to study the impact of one or several covariates on these latent factors. One of the advantages of this model is that it allows for measurement non-invariance, which arises in practice when the factor structure varies between groups of individuals due to cultural or physiological differences. This is achieved by estimating different factor models for different latent classes. The proposed model could also be used to extract latent classes with different latent factor trajectories over time. Other advantages of the model include its ability to take into account heteroscedasticity of errors in the factor analysis model by estimating different error variances for different latent classes. We first define the mixture of longitudinal factor analyzers and its parameters. Then, we propose an EM algorithm to estimate these parameters. We propose a Bayesian information criterion to identify both the number of components in the mixture and the number of latent factors. We then discuss the comparability of the latent factors obtained between subjects in different latent groups. Finally, we apply the model to simulated and real data of patients with chronic postoperative pain.

Evaluation of External Trigeminal Nerve Stimulation to Prevent Cerebral Vasospasm after Subarachnoid Hemorrhage Due to Aneurysmal Rupture: A Randomized, Double-Blind Proof-of-Concept Pilot Trial (TRIVASOSTIM Study).

Cerebral vasospasm remains the most frequent and devastating complication after subarachnoid aneurysmal hemorrhage because of secondary cerebral ischemia and its sequelae. The underlying pathophysiology involves vasodilator peptide release (such as CGRP) and nitric oxide depletion at the level of the precapillary sphincters of the cerebral (internal carotid artery network) and dural (external carotid artery network) arteries, which are both innervated by craniofacial autonomic afferents and tightly connected to the trigeminal nerve and trigemino-cervical nucleus complex. We hypothesized that trigeminal nerve modulation could influence the cerebral flow of this vascular network through a sympatholytic effect and decrease the occurrence of vasospasm and its consequences. We conducted a prospective double-blind, randomized controlled pilot trial to compare the effect of 10 days of transcutaneous electrical trigeminal nerve stimulation vs. sham stimulation on cerebral infarction occurrence at 3 months. Sixty patients treated for aneurysmal SAH (World Federation of Neurosurgical Societies scale between 1 and 4) were included. We compared the radiological incidence of delayed cerebral ischemia (DCI) on magnetic resonance imaging (MRI) at 3 months in moderate and severe vasospasm patients receiving trigeminal nerve stimulation (TNS group) vs. sham stimulation (sham group). Our primary endpoint (the infarction rate at the 3-month follow-up) did not significantly differ between the two groups (p = 0.99). Vasospasm-related infarctions were present in seven patients (23%) in the TNS group and eight patients (27%) in the sham group. Ultimately, we were not able to show that TNS can decrease the rate of cerebral infarction secondary to vasospasm occurrence. As a result, it would be premature to promote trigeminal system neurostimulation in this context. This concept should be the subject of further research.

Stand-alone kyphoplasty in recent thoracolumbar split fractures: A series of 36 patients reviewed at 19months.

INTRODUCTION: Spinal fractures with a split component present specific bone union problems (pseudarthrosis). The purpose of this study was to assess the rate of pseudarthrosis after stand-alone percutaneous kyphoplasties and analyze clinical and radiographic parameters that are predictive of its efficacy in thoracolumbar spine fractures with a split-type of injury. HYPOTHESIS: Stand-alone kyphoplasty results in satisfactory bone union of the treated vertebral body despite the diastasis of fracture fragments. MATERIALS AND METHODS: A retrospective single-center study of 36 patients with posttraumatic monosegmental thoracolumbar vertebral fractures, that were classified as either Magerl A2 or A3.2, without any neurologic deficits. Patients were treated with percutaneous kyphoplasty and PMMA bone cement. The assessment included both clinical (visual analog pain scale [VAS] and Oswestry disability index) and radiographic (pseudarthrosis, fracture gap, disk incarceration, vertebral height and length, and vertebral and regional kyphosis) criteria. RESULTS: A total of 36 patients (mean age 58years) were included, with a mean follow-up of 19.1months. Five of these patients (14%) had a pseudarthrosis. The fracture gap was significantly greater in these patients than in those who had bone union preoperatively (+3.94 mm, p<0.001) and at the last follow-up consultation (+9.3 mm, p<0.001). There was an association between the incarceration of adjacent disks located above (p=0.008) and below (p=0.003) the fracture site and the pseudarthrosis. The mean VAS decreased significantly on the first postoperative day (p<0.001) and remained lower than the initial assessment until the last follow-up (p<0.001). DISCUSSION: Stabilization by stand-alone kyphoplasty produces good clinical and radiographic results for split fractures, provided that the extent of the fragment diastasis has been carefully assessed preoperatively to prevent the risk of pseudarthrosis. LEVEL OF EVIDENCE: IV; retrospective.

"Neuro-Fiber Mapping": An Original Concept of Spinal Cord Neural Network Spatial Targeting Using Live Electrostimulation Mapping to (Re-)Explore the Conus Medullaris Anatomy.

Spinal cord (SC) anatomy is often assimilated to a morphologically encapsulated neural entity, but its functional anatomy remains only partially understood. We hypothesized that it could be possible to re-explore SC neural networks by performing live electrostimulation mapping, based on "super-selective" spinal cord stimulation (SCS), originally designed as a therapeutical tool to address chronic refractory pain. As a starting point, we initiated a systematic SCS lead programming approach using live electrostimulation mapping on a chronic refractory perineal pain patient, previously implanted with multicolumn SCS at the level of the conus medullaris (T12-L1). It appeared possible to (re-)explore the classical anatomy of the conus medullaris using statistical correlations of paresthesia coverage mappings, resulting from 165 different electrical configurations tested. We highlighted that sacral dermatomes were not only located more medially but also deeper than lumbar dermatomes at the level of the conus medullaris, in contrast with classical anatomical descriptions of SC somatotopical organization. As we were finally able to find a morphofunctional description of "Philippe-Gombault's triangle" in 19th-century historical textbooks of neuroanatomy, remarkably matching these conclusions, the concept of "neuro-fiber mapping" was introduced.

Virtual Reality for Decreasing Procedural Pain during Botulinum Toxin Injection Related to Spasticity Treatment in Adults: A Pilot Study.

BACKGROUND AND OBJECTIVES: Botulinum toxin injections are commonly used for the treatment of spasticity. However, injection procedures are associated with pain and procedural anxiety. While pharmacological approaches are commonly used to reduce these, innovative technology might be considered as a potential non-pharmacological alternative. Given this context, immersive virtual reality (VR) has shown effectiveness in the management of procedural pain. Our retrospective pilot study aimed to assess the potential added value of virtual reality in the management of pain and anxiety during intramuscular injections of botulinum toxin. MATERIALS AND METHODS: Seventeen adult patients receiving botulinum toxin injections were included. A numerical rating scale was used to assess pain and anxiety during the injection procedure. The patients reported the pain experienced during previous injections without VR before injection and the pain experienced in the current procedure with VR after the end of the procedure. The level of satisfaction of VR experience, whether or not they agreed to reuse VR for the subsequent toxin botulinum injection, and whether or not they would recommend VR to other patients were assessed. RESULTS: The use of virtual reality led to a decrease of 1.8 pain-related points compared to the procedure without technology. No significant improvement in the level of anxiety was reported. Patients were very satisfied with their VR experiences (7.9 out of 10), and many would agree to reuse VR in their next injection procedure (88%) and to recommend the use of VR in other patients (100%). CONCLUSION: VR was useful for managing procedural pain related to botulinum toxin injection in adults, with a high level of satisfaction reported by the patients. VR should be considered as a valuable alternative to pharmacological approaches to manage procedural pain during botulinum toxin injection in adults.

Combining Awake Anesthesia with Minimal Invasive Surgery Optimizes Intraoperative Surgical Spinal Cord Stimulation Lead Placement.

Spinal cord stimulation (SCS) is an effective and validated treatment to address chronic refractory neuropathic pain in persistent spinal pain syndrome-type 2 (PSPS-T2) patients. Surgical SCS lead placement is traditionally performed under general anesthesia due to its invasiveness. In parallel, recent works have suggested that awake anesthesia (AA), consisting of target controlled intra-venous anesthesia (TCIVA), could be an interesting tool to optimize lead anatomical placement using patient intra-operative feedback. We hypothesized that combining AA with minimal invasive surgery (MIS) could improve SCS outcomes. The goal of this study was to evaluate SCS lead performance (defined by the area of pain adequately covered by paraesthesia generated via SCS), using an intraoperative objective quantitative mapping tool, and secondarily, to assess pain relief, functional improvement and change in quality of life with a composite score. We analyzed data from a prospective multicenter study (ESTIMET) to compare the outcomes of 115 patients implanted with MIS under AA (MISAA group) or general anesthesia (MISGA group), or by laminectomy under general anesthesia (LGA group). All in all, awake surgery appears to show significantly better performance than general anesthesia in terms of patient pain coverage (65% vs. 34-62%), pain surface (50-76% vs. 50-61%) and pain intensity (65% vs. 35-40%), as well as improved secondary outcomes (quality of life, functional disability and depression). One step further, our results suggest that MISAA combined with intra-operative hypnosis could potentialize patient intraoperative cooperation and could be proposed as a personalized package offered to PSPS-T2 patients eligible for SCS implantation in highly dedicated neuromodulation centers.

A 6-Month Home-Based Functional Electrical Stimulation Program for Foot Drop in a Post-Stroke Patient: Considerations on a Time Course Analysis of Walking Performance.

Foot drop is a common disability in post-stroke patients and represents a challenge for the clinician. To date, ankle foot orthosis (AFO) combined with conventional rehabilitation is the gold standard of rehabilitation management. AFO has a palliative mechanical action without actively restoring the associated neural function. Functional electrical stimulation (FES), consisting of stimulation of the peroneal nerve pathway, represents an alternative approach. By providing an FES device (Bioness L-300, BIONESS, Valencia, CA, USA) for 6 months to a post-stroke 22-year-old woman with a foot drop, our goal was to quantify its potential benefit on walking capacity. The gait parameters and the temporal evolution of the speed were collected with a specific connected sole device (Feet Me®) during the 10-m walking, the time up and go, and the 6-minute walking tests with AFO, FES, or without any device (NO). As a result, the walking speed changes on 10-m were clinically significant with an increase from the baseline to 6 months in AFO (+0.14 m.s-1), FES (+0.36 m.s-1) and NO (+0.32 m.s-1) conditions. In addition, the speed decreased at about 4-min in the 6-minute walking test in NO and AFO conditions, while the speed increased in the FES conditions at baseline and after 1, 3, and 6 months. In addition to the walking performance improvement, monitoring the gait speed in an endurance test after an ecological rehabilitation training program helps to examine the walking performance in post-stroke patients and to propose a specific rehabilitation program.

Hypnosis to manage musculoskeletal and neuropathic chronic pain: A systematic review and meta-analysis.

This systematic review and meta-analysis aims to identify and quantify the current available evidence of hypnosis efficacy to manage pain in patients with chronic musculoskeletal and neuropathic pain. Randomized Control Trials (RCTs) with hypnosis and/or self-hypnosis treatment used to manage musculoskeletal and/or neuropathic chronic pain in adults and assessing pain intensity were included. Reviews, meta-analyses, non-randomized clinical trials, case reports and meeting abstracts were excluded. Five databases, up until May 13th 2021, were used to search for RCTs using hypnosis to manage chronic musculoskeletal and/or neuropathic pain. The protocol is registered on PROSPERO register (CRD42020180298) and no specific funding was received for this review. The risk of bias asessement was conducted according to the revised Cochrane risk of bias tool for randomized control trials (RoB 2.0). Nine eligible RCTs including a total of 530 participants were considered. The main analyses showed a moderate decrease in pain intensity (Hedge's g: -0.42; p = 0.025 after intervention, Hedge's g: -0.37; p = 0.027 after short-term follow-up) and pain interference (Hedge's g: -0.39; p = 0.029) following hypnosis compared to control interventions. A significant moderate to large effect size of hypnosis compared to controls was found for at 8 sessions or more (Hedge's g: -0.555; p = 0.034), compared to a small and not statistically significant effect for fewer than 8 sessions (Hedge's g: -0.299; p = 0.19). These findings suggest that a hypnosis treatment lasting a minimum of 8 sessions could offer an effective complementary approach to manage chronic musculoskeletal and neuropathic pain. Future research is needed to delineate the relevance of hypnosis in practice and its most efficient prescription.

The Challenge of Converting "Failed Spinal Cord Stimulation Syndrome" Back to Clinical Success, Using SCS Reprogramming as Salvage Therapy, through Neurostimulation Adapters Combined with 3D-Computerized Pain Mapping Assessment: A Real Life Retrospective Study.

While paresthesia-based Spinal Cord Stimulation (SCS) has been proven effective as treatment for chronic neuropathic pain, its initial benefits may lead to the development of "Failed SCS Syndrome' (FSCSS) defined as decrease over time related to Loss of Efficacy (LoE) with or without Loss of Coverage (LoC). Development of technologies associating new paresthesia-free stimulation waveforms and implanted pulse generator adapters provide opportunities to manage patients with LoE. The main goal of our study was to investigate salvage procedures, through neurostimulation adapters, in patients already implanted with SCS and experiencing LoE. We retrospectively analyzed a cohort of patients who were offered new SCS programs/waveforms through an implanted adapter between 2018 and 2021. Patients were evaluated before and at 1-, 3-, 6- and 12-month follow-ups. Outcomes included pain intensity rating with a Visual Analog Scale (VAS), pain/coverage mappings and stimulation preferences. Last follow-up evaluations (N = 27) showed significant improvement in VAS (p = 0.0001), ODI (p = 0.021) and quality of life (p = 0.023). In the 11/27 patients with LoC, SCS efficacy on pain intensity (36.89%) was accompanied via paresthesia coverage recovery (55.57%) and pain surface decrease (47.01%). At 12-month follow-up, 81.3% preferred to keep tonic stimulation in their waveform portfolio. SCS conversion using adapters appears promising as a salvage solution, with an emphasis on paresthesia recapturing enabled via spatial retargeting. In light of these results, adapters could be integrated in SCS rescue algorithms or should be considered in SCS rescue.

A Novel Multi-Dimensional Clinical Response Index Dedicated to Improving Global Assessment of Pain in Patients with Persistent Spinal Pain Syndrome after Spinal Surgery, Based on a Real-Life Prospective Multicentric Study (PREDIBACK) and Machine Learning Techniques.

The multidimensionality of chronic pain forces us to look beyond isolated assessment such as pain intensity, which does not consider multiple key parameters, particularly in post-operative Persistent Spinal Pain Syndrome (PSPS-T2) patients. Our ambition was to produce a novel Multi-dimensional Clinical Response Index (MCRI), including not only pain intensity but also functional capacity, anxiety-depression, quality of life and quantitative pain mapping, the objective being to achieve instantaneous assessment using machine learning techniques. Two hundred PSPS-T2 patients were enrolled in the real-life observational prospective PREDIBACK study with 12-month follow-up and received various treatments. From a multitude of questionnaires/scores, specific items were combined, as exploratory factor analyses helped to create a single composite MCRI; using pairwise correlations between measurements, it appeared to more accurately represent all pain dimensions than any previous classical score. It represented the best compromise among all existing indexes, showing the highest sensitivity/specificity related to Patient Global Impression of Change (PGIC). Novel composite indexes could help to refine pain assessment by informing the physician's perception of patient condition on the basis of objective and holistic metrics, and also by providing new insights regarding therapy efficacy/patient outcome assessments, before ultimately being adapted to other pathologies.

Professional Status of Persistent Spinal Pain Syndrome Patients after Spinal Surgery (PSPS-T2): What Really Matters? A Prospective Study Introducing the Concept of "Adapted Professional Activity" Inferred from Clinical, Psychological and Social Influence.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2) represents a main cause of work disruption. Beyond its societal consequences, occupational inactivity is responsible for a major decrease in physical/mental health in individuals but remains poorly analyzed. We designed a study to prospectively examine Professional Status (PS) evolution and its association with key bio-psychological markers. Data from 151 consecutively included working-age PSPS-T2 patients were analyzed to determine the proportion of professional inactivity and the relationships between PS and Social Gradient of Health (SGH), Numeric Pain Rating Scale (NPRS), EuroQol 5-Dimensional 5-Level (EQ-5D-5L), Oswestry Disability Index (ODI), Hospital Anxiety and Depression Scale (HADS), and Fear-Avoidance Belief Questionnaire work subscale (FABQ-W). Despite optimized medical management, 73.5% of PSPS-T2 patients remained inactive after 1 year of follow-up/p = 0.18. Inactive patients presented a low SGH/p = 0.002, higher NPRS/p = 0.048, lower EQ-5D-5L/p < 0.001, higher ODI/p = 0.018, higher HADS-D/p = 0.019 and higher FABQ-W/p < 0.001. No significant mediation effect of FABQ-W on SGH consequences regarding PS was observed in our structural model/p = 0.057. The link between unemployment and bio-psycho-social pain dimensions appears bidirectional and justifies intense collaboration with social workers. Optimizing therapeutical sequencing towards personalized professional plans implies restoring "Adapted Physical Function" as an initial goal, and tailoring an "Adapted Professional Activity", matching with patient expectations and capabilities, as a final objective.

The Added Value of Subcutaneous Peripheral Nerve Field Stimulation Combined with SCS, as Salvage Therapy, for Refractory Low Back Pain Component in Persistent Spinal Pain Syndrome Implanted Patients: A Randomized Controlled Study (CUMPNS Study) Based on 3D-Mapping Composite Pain Assessment.

While Spinal Cord Stimulation (SCS) provides satisfaction to almost 2/3 of Persistent Spinal Pain Syndrome-Type 2 (PSPS-T2) patients implanted for refractory chronic back and/or leg pain, when not adequately addressed the back pain component, leaves patients in a therapeutic cul-de-sac. Peripheral Nerve field Stimulation (PNfS) has shown interesting results addressing back pain in the same population. Far from placing these two techniques in opposition, we suggest that these approaches could be combined to better treat PSPS-T2 patients. We designed a RCT (CUMPNS), with a 12-month follow-up, to assess the potential added value of PNfS, as a salvage therapy, in PSPS-T2 patients experiencing a "Failed SCS Syndrome" in the back pain component. Fourteen patients were included in this study and randomized into 2 groups ("SCS + PNfS" group/n = 6 vs. "SCS only" group/n = 8). The primary objective of the study was to compare the percentage of back pain surface decrease after 3 months, using a computerized interface to obtain quantitative pain mappings, combined with multi-dimensional SCS outcomes. Back pain surface decreased significantly greater for the "SCS + PNfS" group (80.2% ± 21.3%) compared to the "SCS only" group (13.2% ± 94.8%) (p = 0.012), highlighting the clinical interest of SCS + PNfS, in cases where SCS fails to address back pain.

Finite Mixture Models Based on Pain Intensity, Functional Disability and Psychological Distress Composite Assessment Allow Identification of Two Distinct Classes of Persistent Spinal Pain Syndrome after Surgery Patients Related to Their Quality of Life.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), (Failed Back Surgery Syndrome), dramatically impacts on patient quality of life, as evidenced by Health-Related Quality of Life (HRQoL) assessment tools. However, the importance of functioning, pain perception and psychological status in HRQoL can substantially vary between subjects. Our goal was to extract patient profiles based on HRQoL dimensions in a sample of PSPS-T2 patients and to identify factors associated with these profiles. Two classes were clearly identified using a mixture of mixed effect models from a clinical data set of 200 patients enrolled in "PREDIBACK", a multicenter observational prospective study including PSPS-T2 patients with one-year follow-up. We observed that HRQoL was more impacted by functional disability for first class patients (n = 136), and by pain perception for second class patients (n = 62). Males that perceive their work as physical were more impacted by disability than pain intensity. Lower education level, lack of adaptive coping strategies and higher pain intensity were significantly associated with HRQoL being more impacted by pain perception. The identification of such classes allows for a better understanding of HRQoL dimensions and opens the gate towards optimized health-related quality of life evaluation and personalized pain management.

Machine Learning Algorithms Provide Greater Prediction of Response to SCS Than Lead Screening Trial: A Predictive AI-Based Multicenter Study.

Persistent pain after spinal surgery can be successfully addressed by spinal cord stimulation (SCS). International guidelines strongly recommend that a lead trial be performed before any permanent implantation. Recent clinical data highlight some major limitations of this approach. First, it appears that patient outco mes, with or without lead trial, are similar. In contrast, during trialing, infection rate drops drastically within time and can compromise the therapy. Using composite pain assessment experience and previous research, we hypothesized that machine learning models could be robust screening tools and reliable predictors of long-term SCS efficacy. We developed several algorithms including logistic regression, regularized logistic regression (RLR), naive Bayes classifier, artificial neural networks, random forest and gradient-boosted trees to test this hypothesis and to perform internal and external validations, the objective being to confront model predictions with lead trial results using a 1-year composite outcome from 103 patients. While almost all models have demonstrated superiority on lead trialing, the RLR model appears to represent the best compromise between complexity and interpretability in the prediction of SCS efficacy. These results underscore the need to use AI-based predictive medicine, as a synergistic mathematical approach, aimed at helping implanters to optimize their clinical choices on daily practice.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), a Social Pain? Advocacy for a Social Gradient of Health Approach to Chronic Pain.

The Social Gradient of Health (SGH), or position in the social hierarchy, is one of the major determinants of health. It influences the development and evolution of many chronic diseases. Chronic pain dramatically affects individual and social condition. Its medico-economic impact is significant and worldwide. Failed Back Surgery Syndrome or Persistent Spinal Pain Syndrome type 2 (PSPS-T2) represents one of its most fascinating and disabling conditions. However, the influence of SGH on PSPS-T2 has been poorly explored. We designed a prospective multicentric study (PREDIBACK study) to assess the SGH prevalence, and to examine its association with medical and psychological variables, in PSPS-T2 patients. This study included 200 patients to determine the SGH association with pain (NPRS), Quality of life (EQ-5D-5L), kinesiophobia (FABQ-Work), catastrophism (CSQ), and functional capacity (ODI). Around 85.3% of PSPS-T2 patients in our study had low SGH. Low SGH patients had a higher FABQ-Work and CSQ-Catastrophizing score than high SGH patients (p < 0.05). High SGH patients have a higher ODI score than low SGH patients (p < 0.10). Our results suggest that SGH is a relevant factor to guide prevention, research, and ultimately intervention in PSPS-T2 patients and could be more widely transposed to chronic pain.

How Should we Use Multicolumn Spinal Cord Stimulation to Optimize Back Pain Spatial Neural Targeting? A Prospective, Multicenter, Randomized, Double-Blind, Controlled Trial (ESTIMET Study).

BACKGROUND: Recent studies have highlighted multicolumn spinal cord stimulation (SCS) efficacy, hypothesizing that optimized spatial neural targeting provided by new-generation SCS lead design or its multicolumn programming abilities could represent an opportunity to better address chronic back pain (BP). OBJECTIVE: To compare multicolumn vs. monocolumn programming on clinical outcomes of refractory postoperative chronic BP patients implanted with SCS using multicolumn surgical lead. MATERIALS AND METHODS: Twelve centers included 115 patients in a multicenter, randomized, double-blind, controlled trial. After randomization, leads were programmed using only one or several columns. The primary outcome was change in BP visual analogic scale (VAS) at six months. All patients were then programmed using the full potential of the lead up until 12-months follow-up. RESULTS: At six months, there was no significant difference in clinical outcomes whether the SCS was programmed using a mono or a multicolumn program. At 12 months, in all patients having been receiving multicolumn SCS for at least six months (n = 97), VAS decreases were significant for global pain (45.1%), leg pain (55.8%), and BP (41.5%) compared with baseline (p < 0.0001). CONCLUSION: The ESTIMET study confirms the significant benefit experienced on chronic BP by patients implanted with multicolumn SCS, independently from multicolumn lead programming. These good clinical outcomes might result from the specific architecture of the multicolumn lead, giving the opportunity to select initially the best column on a multicolumn grid and to optimize neural targeting with low-energy requirements. However, involving more columns than one does not appear necessary, once initial spatial targeting of the "sweet spot" has been achieved. Our findings suggest that this spatial concept could also be transposed to cylindrical leads, which have drastically improved their capability to shape the electrical field, and might be combined with temporal resolution using SCS new modalities.

Comparison of Spinal Cord Stimulation vs. Dorsal Root Ganglion Stimulation vs. Association of Both in Patients with Refractory Chronic Back and/or Lower Limb Neuropathic Pain: An International, Prospective, Randomized, Double-Blinded, Crossover Trial (BOOST-DRG Study).

While spinal cord stimulation (SCS) is a well-established therapy to address refractory persistent spinal pain syndrome after spinal surgery (PSPS-T2), its lack of spatial selectivity and reported discomfort due to positional effects can be considered as significant limitations. As alternatives, new waveforms, such as burst stimulation and different spatial neural targets, such as dorsal root ganglion stimulation (DRGS), have shown promising results. Comparisons between DRGS and standard SCS, or their combination, have never been studied on the same patients. "BOOST DRG" is the first prospective, randomized, double-blinded, crossover study to compare SCS vs. DRGS vs. SCS+DRGS. Sixty-six PSPS-T2 patients will be recruited internationally in three centers. Before crossing over, patients will receive each stimulation modality for 1 month, using tonic conventional stimulation. After 3 months, stimulation will consist in switching to burst for 1 month, and patients will choose which modality/waveform they receive and will then be reassessed at 6 and 12 months. In addition to our primary outcome based on pain rating, this study is designed to assess quality of life, functional disability, psychological distress, pain surface coverage, global impression of change, medication quantification, adverse events, brain functional imaging and electroencephalography, with the objective being to provide a multidimensional insight based on composite pain assessment.

Comparison of conventional, burst and high-frequency spinal cord stimulation on pain relief in refractory failed back surgery syndrome patients: study protocol for a prospective randomized double-blinded cross-over trial (MULTIWAVE study).

BACKGROUND: While the evolution of technology provides new opportunities to manage chronic refractory pain using different waveform modalities of spinal cord stimulation in failed back surgery syndrome (FBSS), there is no randomized controlled trial available to compare the efficacy of these different stimulations waveforms to date. MULTIWAVE is a prospective, randomized, double-blinded, crossover trial study designed to compare the clinical efficacy of tonic conventional stimulation (TCS), burst stimulation (BURST) and high-frequency stimulation (HF) in FBSS patients over a 15-month period in SCS implanted patients. METHODS/DESIGN: Twenty-eight patients will be recruited in the Poitiers University Hospital, in Niort and La Rochelle Hospitals in France. Eligible patients with post-operative low back and leg pain with an average visual analog scale (VAS) score ≥ 5 for low back pain are implanted and randomly assigned to one of the six arms (in a 1:1:1:1:1:1 ratio), where they receive a 3-month combination of TCS, BURST and HF including one treatment modality per month and varying the order of the modality received within the six possible combinations. Patients receiving intrathecal drug delivery, peripheral nerve stimulation and back resurgery related to the original back pain complaint and experimental therapies are excluded from this study. Patients included in the spinal cord stimulation group undergo trial stimulation, and they all receive a TCS treatment for 2 months, as the gold standard modality. Thereafter, patients are randomly assigned to one of the six arms for the total duration of 3-month crossover period. Then, patients choose their preferred stimulation modality (TCS, BURST, or HF) for the follow-up period of 12 months. Outcome assessments are performed at baseline (first implant), before randomization (2 months after baseline) and at 1, 2, 3, 6, 9 and 15 months post-randomization. Our primary outcome is the average global VAS of pain over 5-day pain diary period between baseline and after each period of stimulation. Additional outcomes include changes in leg and back pain intensity, functional disability, quality of life, psychological state, paraesthesia intensity perception, patient satisfaction and the number of adverse events. DISCUSSION: Recruitment began in February 2017 and will continue through 2019. TRIAL REGISTRATION: Clinicaltrials.gov NCT03014583 . Registered on 9 January 2017.

Impact of time to surgery in upper femoral fracture in orthogeriatrics.

INTRODUCTION: Treatment of hip fracture in the elderly is a major public health issue. Orthogeriatric departments have been developed for these patients at high risk of complications. Time to surgery seems to be an important factor in the care pathway, but remains controversial. OBJECTIVES: The aim of this study was to assess the impact of less than 24 hours' time to surgery on 1-year morbidity and mortality in patients managed in our orthogeriatric department. HYPOTHESIS: The study hypothesis was that<24 hours' time to surgery decreases mortality in elderly patients with upper femoral fracture. MATERIALS AND METHODS: A retrospective cohort study from September 2015 to July 2016 included patients aged 75 years and older, eligible for orthogeriatric management of upper femoral fracture. Patients with comorbidities were prioritized for admission and for access to the operating room. Time to surgery was defined as time between the arrival in A&E and transfer to the operating room. The primary endpoint was 1-year survival. Comorbidities were assessed on Charlson score. ROC curve analysis determined the optimal cut-off for time to surgery. Variables significantly associated with mortality were included in a Cox regression model to estimate the adjusted effect of time to surgery on mortality. RESULTS: One hundred and eight patients were included; mean age, 87±6.2 years; 26 male (24.1%), 82 female (75.9%). One-year mortality was 24.1% (26/108). Mean time to surgery was 14.1±30.9hours. ROC curve analysis showed a rise in mortality after a cut-off of 22hours 37minutes (p<0.0001). CONCLUSION: Within a dedicated orthogeriatric department, time to surgery is a significant factor in the management of hip fractures in the elderly. Patients should be prioritized for theater and ideally receive "early" surgery within 24hours of admission to A&E. The potential benefit of "ultra-early" surgery (time to surgery<6hours) requires robust assessment. LEVEL OF EVIDENCE: IV, Retrospective cohort study.