Socioeconomic Determinants of Initiating Neuromodulation for Chronic Pain: A Systematic Review.

OBJECTIVES: Neuromodulation is an effective treatment for chronic pain; however, socioeconomic differences may influence decision-making to initiate this therapy. This review investigated potential differences in accessibility of neuromodulation for patients with chronic pain due to socioeconomic determinants. MATERIALS AND METHODS: Four electronic databases were used for this systematic review: MEDLINE, Embase, Scopus, and Web of Science. Risk of bias was assessed using the modified version of the Downs and Black checklist. The study protocol was prospectively registered on PROSPERO (CRD42023426035). RESULTS: The initial database search identified a total of 1118 unique studies, of which 36 were eventually included in the systematic review. Of the 36 included studies, six studies reported on education, 24 on employment status, ten on insurance, five on household income, and three on miscellaneous topics. Neuromodulation seems accessible for patients with different education levels and different types of insurance. Additionally, it is not restricted to patients who are (un)employed. When comparing patients who initiated neuromodulation with those who did not, a significantly higher number of patients in the top quartile for education were found in the group without neuromodulation. Regarding insurance, inconclusive evidence was found. CONCLUSIONS: Although neuromodulation was accessible for patients with varying levels of socioeconomic determinants, disparities were noted. When comparing the socioeconomic profiles of patients who receive neuromodulation and those who do not, education levels differ. Health-related inequality should be carefully monitored in chronic pain management with neuromodulation to ensure that potential disparities do not increase.

Sleepiness may predict hypnotizability, while personality traits do not.

Sleepiness and personality traits have been controversially reported as associated to individual hypnotizability level i.e. receptiveness to hypnotic suggestions and behave accordingly. In this study, we further investigate the relationship between the level of general daytime sleepiness and personality traits with the level of hypnotizability. Seventy-eight healthy young volunteers (34 women) completed the fast assessment of general daytime sleepiness and personality with the Epworth Sleepiness Scale and the 10-item Big Five Inventory respectively, and underwent hypnotic evaluation through the Harvard Group Scale of Hypnotic Susceptibility Form A (HGSHS:A). Main findings revealed a correlation between sleepiness and hypnotizability levels, and no influence of personality traits. Interestingly, women exhibited higher levels of hypnotizability compared to men. Taken together, these results suggest that sleepiness assessment might be considered as a predictive tool to hypnotic suggestions, which would offer practical insight for enhancing hypnosis intervention efficacy.

Effect of neuromodulation for chronic pain on the autonomic nervous system: a systematic review.

Background: In recent years, there has been a growing interest in the use of neuromodulation as an alternative treatment option for chronic pain. Neuromodulation techniques, such as spinal cord stimulation (SCS), dorsal root ganglion (DRG) stimulation, deep brain stimulation (DBS), and peripheral nerve stimulation, have shown promising results in the management of various chronic pain conditions and involve targeted modulation of neural activity to alleviate pain and restore functional capacity. The autonomic nervous system (ANS) plays a crucial role in the regulation of various bodily functions including pain perception. However, the effects of neuromodulation on the ANS in the context of chronic pain remain poorly understood. This systematic review aimed to comprehensively assess the existing literature about the effects of neuromodulation on the ANS in chronic pain settings. Methods: Searches were conducted using four electronic databases (PubMed, EMBASE, SCOPUS, and Web of Science). The study protocol was registered before initiation of the review process. The Office of Health Assessment and Translation (OHAT) Risk of Bias tool was used to evaluate risk of bias. Results: A total of 43 studies were included, of which only one was an animal study. Several studies have reported more than one outcome parameter in the same population of chronic pain patients. Cardiovascular parameters were the most frequently used outcomes. More specifically, 18 outcome parameters were revealed to evaluate the function of the ANS, namely heart rate variability (n=17), arterial blood pressure (n=15), tissue oxygenation/perfusion (n=5), blood markers (n=6), multiunit postganglionic sympathetic nerve activity (n=4), skin temperature (n=3), skin conductance (n=3), cephalic autonomic symptoms (n=2), ventilatory frequency (n=2), vasomotor tone (n=1), baroreflex sensitivity (n=1), sympathetic innervation of the heart, neural activity of intrinsic cardiac neurons (n=1), vascular conductance (n=1), arterial diameter (n=1), blood pulse volume (n=1), and vagal efficiency (n=1). Most studies evaluated SCS (62.79%), followed by DBS (18.6%), peripheral nerve stimulation (9.3%), DRG stimulation (4.65%), and vagus nerve stimulation (4.65%). Overall, inconsistent results were revealed towards contribution of SCS, DBS, and peripheral nerve stimulation on ANS parameters. For DRG stimulation, included studies pointed towards a decrease in sympathetic activity. Conclusions: There are indications that neuromodulation alters the ANS, supported by high or moderate confidence in the body of evidence, however, heterogeneity in ANS outcome measures drives towards inconclusive results. Further research is warranted to elucidate the indirect or direct mechanisms of action on the ANS, with a potential benefit for optimisation of patient selection for these interventions. Systematic review protocol: PROSPERO (CRD42021297287).

ANKLE TORQUE VARIANCE IS A BETTER INDICATOR OF BALANCE CONTROL PERFORMANCE THAN PLANTAR PERCEPTUAL SENSITIVITY THRESHOLD.

We explored whether ankle torque variability or plantar perceptual threshold explains human balance control more effectively. We hypothesized that ankle torque variance is a better indicator of center of pressure (COP) velocity variance than plantar perceptual sensitivity. Two conditions were tested: loaded (23 kg vest added) and unloaded, as loading should diminish plantar sensitivity and increase COP velocity variability. We created a linear feedback model to assess the noise change in the sensorimotor loop induced by loading. Plantar sensitivity was quantified using a psychophysical approach while participants stood barefoot. A linear motor applied a force impulse on the participant's heel. A 'yes-no' method of limits was selected to identify plantar sole sensory thresholds in both conditions. We observed reduced plantar sensitivity in loaded compared to unloaded conditions. In the loaded condition, participants exhibited greater COP velocity variance, with significant positive Pearson's correlations confirming a substantial association between ankle torque and COP velocity variances for both loaded (variance accounted for (VAR): r2 = 44.56%, p = 0.018) and unloaded conditions (VAF: r2 = 58.83 %, p = 0.004). No significant correlation existed between COP velocity variance and plantar sensitivity threshold for both loaded (VAF: r2 = 0.002 %, p = 0.99) and unloaded conditions (VAF: r2 = 21.81%, p = 0.35). The model confirmed a ~88% rise in sensorimotor loop noise in the loaded condition. Ankle torque variance assesses the precision of non-perceptual and perceptual detection mechanisms in evaluating whole-body motions and the accuracy in converting sensory cues into ankle torque.

The value of action observation in speech and language rehabilitation: A systematic review and meta-analysis.

In this systematic review and meta-analysis, our aim was to identify and quantify evidence of action observation therapy (AOT) efficacy in managing language deficits in patients with aphasia. This study conducts two quantitative investigations: firstly, comparing the effects of AOT and conventional control therapy in different groups, and secondly, analyzing within AOT group to explore potential moderators of AOT effectiveness. Four databases were searched up until August 2023 to find studies utilizing AOT for aphasia management. Seven eligible studies were included. The main analyses revealed moderate evidence of improvement in naming tasks, with a large effect size (Hedge's g = 1.27, 95 %CI [0.44; 2.09], p = 0.003, I2 < 25) following AOT compared to control interventions. Furthermore, to be efficient, AOT should focus on human actions (e.g., running, jumping) rather than non-human actions (e.g., meowing or barking). These findings indicate that AOT is a promising alternative complementary approach for patients with aphasia. Future research should confirm the potential benefits of AOT with more randomized controlled studies and aim to clarify the minimal dose necessary and the possibility of transfer to various language tasks.

Gut dysbiosis in patients with chronic pain: a systematic review and meta-analysis.

Introduction: Recent evidence supports the contribution of gut microbiota dysbiosis to the pathophysiology of rheumatic diseases, neuropathic pain, and neurodegenerative disorders. The bidirectional gut-brain communication network and the occurrence of chronic pain both involve contributions of the autonomic nervous system and the hypothalamic pituitary adrenal axis. Nevertheless, the current understanding of the association between gut microbiota and chronic pain is still not clear. Therefore, the aim of this study is to systematically evaluate the existing knowledge about gut microbiota alterations in chronic pain conditions. Methods: Four databases were consulted for this systematic literature review: PubMed, Web of Science, Scopus, and Embase. The Newcastle-Ottawa Scale was used to assess the risk of bias. The study protocol was prospectively registered at the International prospective register of systematic reviews (PROSPERO, CRD42023430115). Alpha-diversity, ß-diversity, and relative abundance at different taxonomic levels were summarized qualitatively, and quantitatively if possible. Results: The initial database search identified a total of 3544 unique studies, of which 21 studies were eventually included in the systematic review and 11 in the meta-analysis. Decreases in alpha-diversity were revealed in chronic pain patients compared to controls for several metrics: observed species (SMD= -0.201, 95% CI from -0.04 to -0.36, p=0.01), Shannon index (SMD= -0.27, 95% CI from -0.11 to -0.43, p<0.001), and faith phylogenetic diversity (SMD -0.35, 95% CI from -0.08 to -0.61, p=0.01). Inconsistent results were revealed for beta-diversity. A decrease in the relative abundance of the Lachnospiraceae family, genus Faecalibacterium and Roseburia, and species of Faecalibacterium prausnitzii and Odoribacter splanchnicus, as well as an increase in Eggerthella spp., was revealed in chronic pain patients compared to controls. Discussion: Indications for gut microbiota dysbiosis were revealed in chronic pain patients, with non-specific disease alterations of microbes. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023430115.

Improved Outcomes and Therapy Longevity after Salvage Using a Novel Spinal Cord Stimulation System for Chronic Pain: Multicenter, Observational, European Case Series.

Spinal cord stimulation (SCS) is proven to effectively relieve chronic neuropathic pain. However, some implanted patients may face loss of efficacy (LoE) over time, and conversion to more recent devices may rescue SCS therapy. Recent SCS systems offer novel stimulation capabilities, such as temporal modulation and spatial neural targeting, and can be used to replace previous neurostimulators without changing existing leads. Our multicenter, observational, consecutive case series investigated real-world clinical outcomes in previously implanted SCS patients who were converted to a new implantable pulse generator. Data from 58 patients in seven European centers were analyzed (total follow-up 7.0 years, including 1.4 years after conversion). In the Rescue (LoE) subgroup (n = 51), the responder rate was 58.5% at the last follow-up, and overall pain scores (numerical rating scale) had decreased from 7.3 ± 1.7 with the previous SCS system to 3.5 ± 2.5 (p < 0.0001). Patients who converted for improved battery longevity (n = 7) had their pain scores sustained below 3/10 with their new neurostimulator. Waveform preferences were diverse and patient dependent (34.4% standard rate; 44.8% sub-perception modalities; 20.7% combination therapy). Our results suggest that patients who experience LoE over time may benefit from upgrading to a more versatile SCS system.

Examining the Type, Quality, and Content of Web-Based Information for People With Chronic Pain Interested in Spinal Cord Stimulation: Social Listening Study.

BACKGROUND: The increased availability of web-based medical information has encouraged patients with chronic pain to seek health care information from multiple sources, such as consultation with health care providers combined with web-based information. The type and quality of information that is available on the web is very heterogeneous, in terms of content, reliability, and trustworthiness. To date, no studies have evaluated what information is available about neuromodulation on the web for patients with chronic pain. OBJECTIVE: This study aims to explore the type, quality, and content of web-based information regarding spinal cord stimulation (SCS) for chronic pain that is freely available and targeted at health care consumers. METHODS: The social listening tool Awario was used to search Facebook (Meta Platforms, Inc), Twitter (Twitter, Inc), YouTube (Google LLC), Instagram (Meta Platforms, Inc), blogs, and the web for suitable hits with "pain" and "neuromodulation" as keywords. Quality appraisal of the extracted information was performed using the DISCERN instrument. A thematic analysis through inductive coding was conducted. RESULTS: The initial search identified 2174 entries, of which 630 (28.98%) entries were eventually withheld, which could be categorized as web pages, including news and blogs (114/630, 18.1%); Reddit (Reddit, Inc) posts (32/630, 5.1%); Vimeo (Vimeo, Inc) hits (38/630, 6%); or YouTube (Google LLC) hits (446/630, 70.8%). Most posts originated in the United States (519/630, 82.4%). Regarding the content of information, 66.2% (383/579) of the entries discussed (fully discussed or partially discussed) how SCS works. In total, 55.6% (322/579) of the entries did not elaborate on the fact that there may be >1 potential treatment choice and 47.7% (276/579) did not discuss the influence of SCS on the overall quality of life. The inductive coding revealed 4 main themes. The first theme of pain and the burden of pain (1274/8886, 14.34% coding references) explained about pain, pain management, individual impact of pain, and patient experiences. The second theme included neuromodulation as a treatment approach (3258/8886, 36.66% coding references), incorporating the background on neuromodulation, patient-centered care, SCS therapy, and risks. Third, several device-related aspects (1722/8886, 19.38% coding references) were presented. As a final theme, patient benefits and testimonials of treatment with SCS (2632/8886, 29.62% coding references) were revealed with subthemes regarding patient benefits, eligibility, and testimonials and expectations. CONCLUSIONS: Health care consumers have access to web-based information about SCS, where details about the surgical procedures, the type of material, working mechanisms, risks, patient expectations, testimonials, and the potential benefits of this therapy are discussed. The reliability, trustworthiness, and correctness of web-based sources should be carefully considered before automatically relying on the content.

Effectiveness of Virtual Reality and Feedback to Improve Gait and Balance in Patients with Diabetic Peripheral Neuropathies: Systematic Review and Meta-Analysis.

Diabetic peripheral neuropathy (DPN) is the primary complication in patients with diabetes mellitus, characterized by loss of sensation and function in the lower limbs. Virtual reality (VR) and/or sensory feedback (FB) therapy has shown positive effects in other neurologic conditions such as stroke. However, consensus regarding their effectiveness in the DPN population is lacking. This study aims to analyze existing scientific evidence about the effects of VR and/or FB on improving gait and balance and reducing the risk of falls in patients with DPN (pwDPN). A thorough search was conducted in scientific databases including PubMed, Scopus, and EMBASE, up until November 2023. CMSQ, the PEDro scale, and the Cochrane Collaboration's tool were used to assess the methodological quality and risk of bias of the studies. A total of 10 studies were selected for qualitative analysis, with three contributing information to the meta-analysis. The combined results suggest a positive trend in favor of VR and FB rehabilitation; however, significant differences were not observed in balance (SMD = -0.81, 95% CI = -1.90, 0.29; p = 0.15; I2 = 86%) or gait speed improvements (MD = -1.05, 95% CI = -2.96, 0.85; p = 0.28; I2 = 89%). Therefore, further randomized controlled studies are still needed to achieve stronger conclusions regarding the benefits of VR and/or FB in pwDPN.

Management of post-traumatic stress disorder symptoms by yoga: an overview.

BACKGROUND: Posttraumatic stress disorder (PTSD) can occur after trauma. While PTSD management strategies include first-line pharmacotherapy and psychotherapy, mind-body therapies, such as yoga, are applied in the PTSD population. This overview aimed to summarize the effectiveness of yoga interventions on PTSD symptoms in adults in a systematic review (SR) including randomized controlled trials (RCTs). METHOD: We searched for SR with or without meta-analysis of RCTs involving adults with PTSD diagnosis or trauma history. The search was conducted until April 2022, through six databases (Cochrane Database, MEDLINE (Pubmed), Scopus, Embase, CINHAL and PEDro). The primary outcome was the evolution of PTSD symptoms throughout the intervention. Secondary outcomes included follow-up, safety, adherence, and cost of the intervention. Two authors independently performed the selection, data extraction and risk of bias assessment with the AMSTAR 2 tool and overlap calculation. This overview is a qualitative summary of the results obtained in the selected studies. RESULTS: Eleven SRs were analyzed, of which 8 included meta-analyses. The overlap between studies was considered very high (corrected covered area of 21%). Fifty-nine RCTs involving 4434 participants were included. Yoga had a significant small-to-moderate effect-size on PTSD symptom decrease in 7 SRs and non-significant effects in 1 SR with meta-analysis. All SR without meta-analysis found beneficial effects of yoga on PTSD. Secondary outcomes were not sufficiently assessed to provide clear evidence. Results should be interpreted with caution as 1 SR was rated as at moderate risk of bias, 3 as low and 7 as critically low. CONCLUSIONS: While yoga therapy seems promising for decreasing PTSD symptoms, future research should standardize yoga therapy duration/frequency/type and consider long-term efficacy to better delineate yoga therapy efficacy in PTSD patients.

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.

Is Spinal Cord Stimulation Still Effective After One or More Surgical Revisions?

OBJECTIVES: Spinal cord stimulation (SCS) is burdened with surgical complications that may require one or several surgical revision(s), challenging its risk/benefit ratio and cost-effectiveness. Our objective was to evaluate its outcome and efficacy after one or more SCS surgical revisions. MATERIALS AND METHODS: We identified and retrospectively analyzed 116 patients treated by tonic paresthesia-based SCS who experienced one or more complication(s) requiring at least one surgical revision. Data collected included initial indication, revision indication, number of revisions, and lead design (paddle or percutaneous). Outcome after SCS revision was evaluated by pain intensity decrease (comparing baseline and postrevision Numerical Rating Scale [NRS] scores) and percentage of patients reporting pain relief ≥50%. Outcome was analyzed according to the number of surgical revisions and the revision indications. RESULTS: Most of the patients (61%) underwent only one revision (mean delay after implantation 44 months). The most frequent causes of revisions were hardware dysfunction (32%), lead migration (23%), and infection (18%). Revision(s) repaired the SCS issue in 87% of the cases. One year after the first revision, 82% of the patients reported pain relief ≥50%, and the mean NRS decrease was 4.0 compared with baseline (p < 0.001). Benefit of SCS revision tended to decrease with the number of revisions but did not differ across revision indications. No serious surgical complications related to the revision occurred, except for three hematomas occurring after repeated revisions. CONCLUSIONS: Our data suggest that surgical revision of SCS system is safe and led to significant pain relief in most of the cases, provided that the initial indication was good and that the previous stimulation was effective. However, success of SCS revision decreases with the number of revisions.

Point-light display: a new tool to improve verb recovery in patients with aphasia? A pilot study.

Some studies have demonstrated that Action Observation (AO) could help patients with aphasia to recover use of verbs. However, the role of kinematics in this effect has remained unknown. The main aim was to assess the effectiveness of a complementary intervention based on the observation of action kinematics in patients with aphasia. Seven aphasic patients (3 males, 4 females) aged between 55 and 88 years participated in the studies. All patients received a classical intervention and an additional, specific intervention based on action observation. This consisted in visualizing a static image or a point-light sequence representing a human action and in trying to name the verb representing the action. In each session, 57 actions were visualized: 19 represented by a static drawing, 19 by a non-focalized point-light sequence, i.e., a point-light display with all dots in white, and 19 by a focalized point-light sequence, i.e., a point-light display (PLD) with the dots corresponding to the main limbs in yellow. Before (pre-test) and after (post-test) the intervention, each patient performed the same denomination task, in which all actions were presented in photographs. The results showed a significant improvement in performance between pre and post-test, but only when the actions were presented in focalized and non-focalized point-light sequences during the intervention. The presentation of action kinematics seems crucial in the recovery of verbs in patients with aphasia. This should be considered by speech therapists in their interventions.

"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.

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.

Heart rate variability is not suitable as a surrogate marker for pain intensity in patients with chronic pain.

ABSTRACT: The search towards more objective outcome measurements and consequently surrogate markers for pain started decades ago; however, no generally accepted biomarker for pain has qualified yet. The goal is to explore the value of heart rate variability (HRV) as surrogate marker for pain intensity chronic pain setting. Pain intensity scores and HRV were collected in 366 patients with chronic pain, through a cross-sectional multicenter study. Pain intensity was measured with both the visual analogue scale and numeric rating scale, whereas 16 statistical HRV parameters were derived. Canonical correlation analysis was performed to evaluate the correlation between the dependent pain variables and the HRV parameters. Surrogacy was determined for each HRV parameter with point estimates between 0 and 1 whereby values close to 1 indicate a strong association between the surrogate and the true endpoint at the patient level. Weak correlations were revealed between HRV parameters and pain intensity scores. The highest surrogacy point estimate was found for mean heart rate as marker for average pain intensity on the numeric rating scale with point estimates of 0.0961 (95% confidence interval [CI] 0.0384-0.1537) and 0.0209 (95% CI 0-0.05) for patients without medication use and with medication, respectively. This study indicated that HRV parameters as separate entities are no suitable surrogacy candidates for pain intensity, in a population of chronic pain patients. Further potential surrogate candidates and clinical robust true endpoints should be explored, to find a surrogate measure for the highly individual pain experience.

Proportion of clinical holistic responders in patients with persistent spinal pain syndrome type II treated by subthreshold spinal cord stimulation compared to best medical treatment: a study protocol for a multicentric randomised controlled trial (TRADITION).

BACKGROUND: Integrating information on bodily functions, pain intensity and quality of life into one composite measure of a holistic responder has recently been proposed as a useful method to evaluate treatment efficacy of spinal cord stimulation (SCS) in patients with therapy-refractory persistent spinal pain syndrome type II (PSPS-T2). Previous studies already demonstrated the efficacy of standard SCS over best medical treatment (BMT) and the superiority of new subthreshold (i.e. paresthesia free) SCS paradigms compared to standard SCS. Nevertheless, the efficacy of subthreshold SCS compared to BMT has not yet been investigated in patients with PSPS-T2, neither with unidimensional outcomes nor with a composite measure. The current objective is to examine whether subthreshold SCS, compared to BMT, provided to patients with PSPS-T2 results in a different proportion of clinical holistic responders (as composite measure) at 6 months. METHODS: A two-arm multicentre randomised controlled trial will be conducted whereby 114 patients will be randomised (1:1) to (a) BMT or (b) paresthesia-free SCS. After a follow-up period of 6 months (primary time endpoint), patients receive the opportunity to cross over towards the other treatment group. The primary outcome is the proportion of clinical holistic responders at 6 months (i.e. a composite measure of pain intensity, medication, disability, health-related quality of life and patient satisfaction). The secondary outcomes are work status, self-management, anxiety, depression and healthcare expenditure. DISCUSSION: Within the TRADITION project, we propose to shift the focus from a unidimensional outcome measure towards a composite measure as primary outcome measure to evaluate the efficacy of currently used subthreshold SCS paradigms. The lack of methodologically rigorous trials exploring the clinical efficacy and socio-economic consequences of subthreshold SCS paradigms is pressing, especially in light of the growing burden of PSPS-T2 on the society. TRIAL REGISTRATION: ClinicalTrials.gov NCT05169047. Registered on December 23, 2021.