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.

"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.

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.

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.

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.

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.