Ten-kHz Spinal Cord Stimulation vs Radiofrequency Ablation of Splanchnic Nerves: A Single-Site Retrospective Comparison of 12-Month Outcomes.

OBJECTIVES: A prospective study on 10-kHz spinal cord stimulation (SCS) for various causes of chronic abdominal pain (CAP) showed robust improvements in subjects' pain and function. Radiofrequency ablation of splanchnic nerves (snRFA) has been used in advanced pain management treatment algorithms for CAP. This analysis was designed to provide what we believe is the first comparison of the efficacy of these two therapies. Propensity-score matched analysis (PMA) was performed to compare pain relief and decrease in medication usage in snRFA and SCS for treating refractory CAP. MATERIALS AND METHODS: Medical records were extracted for consecutive patients with CAP treated from June 2015 to June 2021 who underwent either snRFA or SCS at the Carolinas Pain Institute after positive diagnostic splanchnic block. The patients' diagnoses included gastroparesis, chronic pancreatitis, postsurgical CAP, and other dysmotility syndromes. PMA was performed to produce matched pairs in terms of baseline clinical status, reported pain, and opioid use over 12 months, after treatment was compared in the groups. RESULTS: PMA produced two well-balanced groups (n = 31) for SCS and snRFA. Analysis showed significant improvement in pain scores in both groups through 12 months, but the mean reduction in reported numerical rating scale points was significantly greater for the SCS group, averaging 4.7 vs 3.0 points for the snRFA group (p < 0.01). Responder rates (≥50% pain relief) similarly diverged at 12 months, with 67.7% vs 30.0% responders in the SCS and snRFA groups, respectively (p = 0.017). Opioid usage did not change in the snRFA group but was reduced in the SCS group at 12 months (p = 0.004). CONCLUSIONS: SCS provided longer pain relief than did snRFA in this propensity-matched study. Pain scores and opioid usage were significantly less at 12-month follow-up when SCS was used for control of CAP.

A preliminary study exploring the effects of transcutaneous spinal cord stimulation on spinal excitability and phantom limb pain in people with a transtibial amputation.

OBJECTIVE: Phantom limb pain (PLP) is debilitating and affects over 70% of people with lower-limb amputation. Other neuropathic pain conditions correspond with increased spinal excitability, which can be measured using reflexes and F-waves. Spinal cord neuromodulation can be used to reduce neuropathic pain in a variety of conditions and may affect spinal excitability, but has not been extensively used for treating phantom limb pain. Here, we propose using a non-invasive neuromodulation method, transcutaneous spinal cord stimulation (tSCS), to reduce PLP and modulate spinal excitability after transtibial amputation. Approach: We recruited three participants, two males (5- and 9-years post-amputation, traumatic and alcohol-induced neuropathy) and one female (3 months post-amputation, diabetic neuropathy) for this 5-day study. We measured pain using the McGill Pain Questionnaire, visual analog scale (VAS), and pain pressure threshold test. We measured spinal reflex and motoneuron excitability using posterior root-muscle (PRM) reflexes and F-waves, respectively. We delivered tSCS for 30 minutes/day for 5 days. Main Results: After 5 days of tSCS, McGill Pain Questionnaire scores decreased by clinically-meaningful amounts for all participants from 34.0±7.0 to 18.3±6.8; however, there were no clinically-significant decreases in VAS scores. Two participants had increased pain pressure thresholds across the residual limb (Day 1: 5.4±1.6 lbf; Day 5: 11.4±1.0 lbf). F-waves had normal latencies but small amplitudes. PRM reflexes had high thresholds (59.5±6.1 µC) and low amplitudes, suggesting that in PLP, the spinal cord is hypoexcitable. After 5 days of tSCS, reflex thresholds decreased significantly (38.6±12.2 µC; p<0.001). Significance: These preliminary results in this non-placebo-controlled study suggest that, overall, limb amputation and PLP may be associated with reduced spinal excitability and tSCS can increase spinal excitability and reduce PLP.

The MuscleSCS Technique (4-8Hz BurstDRTM Octrode™): A Randomized Clinical Study of MuscleSCS Stimulation in the Treatment of Chronic Back Pain.

BACKGROUND: MuscleSCS is a new technique that combines spinal cord stimulation (SCS) with muscle stimulation to relieve pain. OBJECTIVES: In this clinical study, we wanted to use rod electrodes to investigate the MuscleSCS method's effectiveness in the treatment of chronic lower back pain. One of our hypotheses was that the combined use of MuscleSCS and BurstDRTM would further improve the treatment. STUDY DESIGN: A prospective, single-center, single-blinded, randomized crossover study. SETTING: A university medical center. METHODS: Patients with chronic lower back pain had previously (one to 10 years ago) received an SCS system (Octrode™). In this study, they were randomly treated for 2 weeks each with BurstDRTM stimulation alone, MuscleSCS stimulation alone, or a combination of BurstDRTM stimulation and MuscleSCS stimulation. Thereafter, the patients were treated for another 6 weeks with one of the 3 methods (crossover possible). Pain ratings on the visual analog scale (VAS) were recorded and compared. A Pain Disability Index (PDI) questionnaire was used at the baseline and at 3 months. RESULTS: We included 24 patients in this study (11 women, mean age 62.3 yrs.) The values of the second week of the stimulation were the only ones used for the calculations. The first week of the stimulation was used as a wash-out period.The combined application of BurstDRTM and MuscleSCS stimulation was associated with the best results (P = 0.032). PDI scores did not improve during this treatment. No serious adverse events occurred during this study. Seventy-one and a half percent of the patients experienced an improvement in their pain as a result of the additional MuscleSCS stimulation. LIMITATIONS: In this study, only one fixed contact setting (3 & 4) was used to ensure uniform conditions for all patients and the ability to compare the different treatment modes. CONCLUSION: This study showed that the combined application of SCS (BurstDRTM) and additional MuscleSCS stimulation using a rod electrode could significantly improve outcomes for patients suffering from chronic back pain.

Percutaneous Endoscope-assisted Visualized Implantation of Puncture Cylindrical Electrodes for Spinal Cord Stimulation: A Cadaveric Feasibility Study.

BACKGROUND: Spinal cord stimulation is an established technique wherein diverse electrode types are strategically implanted within the spinal epidural space for neuromodulation. Traditional percutaneous puncture cylindrical electrodes (PEs) are predominantly implanted by interventionalists utilizing a percutaneous technique under the monitor of radiation, which is a nonvisualized procedure. OBJECTIVE: Our study aimed to assess the feasibility of percutaneous endoscope-assisted visualized implantation approach for PEs, delineating its specific merits and demerits compared to the traditional method. STUDY DESIGN: Laboratory study with Institutional Review Board Number B2023-056SETTING: Clinical Anatomy Research Center, Fudan University. METHODS: Eight freshly procured adult cadavers (4 women and 4 men) were operated on in this study. They were divided into either Group A or Group B, each encompassing 4 cadavers. Group A was subjected to endoscope-assisted PEs implantation, whereas Group B followed the conventional PEs implantation route.In both groups the operative time of introducer needles placement (OTNP), total operative time (TOT), fluoroscopy time of introducer needles placement (FTNP), and total fluoroscopy time (TFT) were documented and analyzed. Furthermore, the precise positioning of the PEs and any ensuing complications were systematically examined. RESULTS: Both Group A and Group B successfully executed all predetermined surgical steps. A total of 16 PEs were implanted (dual electrodes in each cadaver): 8 using the percutaneous endoscope-assisted visualized approach (Group A) and 8 via the traditional methodology (Group B). Group A's mean ± SD durations for OTNP, TOT, FTNP, and TFT were 10.25 ± 1.03 minutes, 31.63 ± 5.87 minutes, 4.58 ± 1.35 seconds, and 43.73 ± 14.46 seconds, respectively. In contrast, Group B exhibited mean ± SD times of 11.55 ± 2.81 minutes, 44.75 ± 7.85 minutes, 23.53 ± 4.16 seconds, and 66.30 ± 6.35 seconds for the same metrics. No discernible statistical difference in OTNP and TOT emerged between the groups. However, Group A demonstrated reduced durations for both FTNP and TFT compared to Group B. The optimal position of the PEs was verified via fluoroscopy, with no recorded instances of dura rupture. These outcomes suggest that this endoscope-assisted technique neither increases surgical time nor compromises efficacy. Instead, it leads to a marked reduction in fluoroscopic duration relative to the traditional methodology. LIMITATIONS: Anatomical study on a human cadaver, the quantity of cadavers, and the procedure's steep learning curve. CONCLUSION: With the assistance of percutaneous spinal endoscopy, introducer needles can be punctured through the ligamentum flavum at the anticipated interlaminar window locus under direct visualization, improving the convenience of the puncture and reducing fluoroscopic exposure. It is a viable alternative for surgeons from diverse training backgrounds to implant PEs, particularly benefiting those well-versed in endoscopic spine surgery techniques.

Long-term explantation risk in patients with chronic pain treated with spinal cord or dorsal root ganglion stimulation.

OBJECTIVE: To investigate long-term explantation risks and causes for the explantation of neuromodulation devices for the treatment of chronic pain from different manufacturers. METHODS: This retrospective analysis included patients implanted with a system for spinal cord stimulation (SCS) or dorsal root ganglion (DRG) stimulation at Sahlgrenska University Hospital between January 2012 and December 2022. Patient characteristics, explantation rates and causes for explantation were obtained by reviewing medical records. RESULTS: In total, 400 patients were included in the study. Including all manufacturers, the cumulative explantation risk for any reason was 17%, 23% and 38% at 3, 5 and 10 years, respectively. Explantation risk due to diminished pain relief at the same intervals was 10%, 14% and 23%. A subgroup comparison of 5-year explantation risk using Kaplan-Meier analysis did not show a statistically significant difference between the manufacturers. In multivariable Cox regression analyses, there was no difference in explantation risk for any reason, but for explantation due to diminished pain relief, a higher risk was noted for Medtronic (preferably older types of SCS devices) and DRG stimulation. No other predictive factor for explantation was found. CONCLUSIONS: Although SCS and DRG stimulation are well-established and safe treatments for chronic pain, the long-term explantation risk remains high. The difference between manufacturers highlights the importance of technological evolution for improving therapy outcomes. Increased stringency in patient selection and follow-up strategies, as well as further development of device hardware and software technology for increased longevity, could possibly reduce long-term explantation risks.

Pharmacologic, Surgical, and Device-Based Cardiac Neuromodulation.

The cardiac autonomic nervous system plays a key role in maintaining normal cardiac physiology, and once disrupted, it worsens the cardiac disease states. Neuromodulation therapies have been emerging as new treatment options, and various techniques have been introduced to mitigate autonomic nervous imbalances to help cardiac patients with their disease conditions and symptoms. In this review article, we discuss various neuromodulation techniques used in clinical settings to treat cardiac diseases.

Interactions between arm and leg neuronal circuits following paired cervical and lumbosacral transspinal stimulation in healthy humans.

Transspinal (or transcutaneous spinal cord) stimulation is a promising noninvasive method that may strengthen the intrinsic spinal neural connectivity in neurological disorders. In this study we assessed the effects of cervical transspinal stimulation on the amplitude of leg transspinal evoked potentials (TEPs), and the effects of lumbosacral transspinal stimulation on the amplitude of arm TEPs. Control TEPs were recorded following transspinal stimulation with one cathode electrode placed either on Cervical 3 (21.3 ± 1.7 mA) or Thoracic 10 (23.6 ± 16.5 mA) vertebrae levels. Associated anodes were placed bilaterally on clavicles or iliac crests. Cervical transspinal conditioning stimulation produced short latency inhibition of TEPs recorded from left soleus (ranging from - 6.11 to -3.87% of control TEP at C-T intervals of -50, -25, -20, -15, -10, 15 ms), right semitendinosus (ranging from - 11.1 to -4.55% of control TEP at C-T intervals of -20, -15, 15 ms), and right vastus lateralis (ranging from - 13.3 to -8.44% of control TEP at C-T intervals of -20 and - 15 ms) (p < 0.05). Lumbosacral transspinal conditioning stimulation produced no significant effects on arm TEPs. We conclude that in the resting state, cervical transspinal stimulation affects the net motor output of leg motoneurons under the experimental conditions used in this study. Further investigations are warranted to determine whether this protocol may reactivate local spinal circuitry after stroke or spinal cord injury and may have a significant effect in synchronization of upper and lower limb muscle synergies during rhythmic activities like locomotion or cycling.

Identifying SCS Trial Responders Immediately After Postoperative Programming with ECAP Dose-Controlled Closed-Loop Therapy.

INTRODUCTION: Drawbacks of fixed-output spinal cord stimulation (SCS) screening trials may lead to compromised trial outcomes and poor predictability of long-term success. Evoked compound action potential (ECAP) dose-controlled closed-loop (CL) SCS allows objective confirmation of therapeutic neural activation and pulse-to-pulse stimulation adjustment. We report on the immediate patient-reported and neurophysiologic treatment response post-physiologic CL-SCS and feasibility of early SCS trial responder prediction. METHODS: Patient-reported pain relief, functional improvement, and willingness to proceed to permanent implant were compared between the day of the trial procedure (Day 0) and end of trial (EOT) for 132 participants in the ECAP Study undergoing a trial stimulation period. ECAP-based neurophysiologic measurements from Day 0 and EOT were compared between responder groups. RESULTS: A high positive predictive value (PPV) was achieved with 98.4% (60/61) of patients successful on the Day 0 evaluation also responding at EOT. The false-positive rate (FPR) was 5.6% (1/18). ECAP-based neurophysiologic measures were not different between patients who passed all Day 0 success criteria ("Day 0 successes") and those who did not ("needed longer to evaluate the therapy"). However, at EOT, responders had higher therapeutic usage and dose levels compared to non-responders. CONCLUSIONS: The high PPV and low FPR of the Day 0 evaluation provide confidence in predicting trial outcomes as early as the day of the procedure. Day 0 trials may be beneficial for reducing patient burden and complication rates associated with extended trials. ECAP dose-controlled CL-SCS therapy may provide objective data and rapid-onset pain relief to improve prognostic ability of SCS trials in predicting outcomes. TRIAL REGISTRATION: The ECAP Study is registered with ClinicalTrials.gov (NCT04319887).

Does Spinal Cord Stimulation Improve Sleep Disturbances Independently of Pain Relief in Patients With Chronic Pain? An Explorative, Observational Study.

OBJECTIVES: Chronic pain poses a significant health challenge worldwide and is associated with both disability and reduced quality of life. Sleep disturbances are reported in 67% to 88% of patients with chronic pain. Pain and sleep affect each other reciprocally; we aimed to study this bidirectional relationship in patients treated with spinal cord stimulation (SCS) for chronic pain. Specifically, we investigated whether sleep improves after treatment with SCS and whether this improvement may be mediated by pain reduction. MATERIALS AND METHODS: An observational cohort study was conducted in patients with chronic neuropathic pain treated with SCS at a single neurosurgical department in Denmark. Outcomes were assessed preoperatively and at three, six, and 12 months postoperatively, and thereafter annually. Primary outcomes were pain intensity (numeric rating scale) and insomnia at first follow-up (Insomnia Severity Index). The association between sleep and pain was investigated using linear regression and mediation analysis. RESULTS: Forty-three patients were included in the study. The mean insomnia score was reduced by 25% from 18.1 (SD 6.0) to 13.5 (SD 6.6) (p = 0.0001). Pain intensity was reduced 38% from 7.4 (SD 1.6) to 4.6 (SD 2.1) at the first follow-up (p ≤ 0.0001). Changes in pain and changes in insomnia scores were significantly but weakly associated (regression coefficient = 1.3, 95% CI [0.3; 2.2], p = 0.008, r2 = 15.7%); and changes in pain score were not found to mediate changes in sleep score (ß = -0.02, 95% CI [-0.15; 0.11], p = 0.76). CONCLUSIONS: We found that patients treated with SCS showed significant improvements in both insomnia and pain intensity at first follow-up. Improvements in insomnia and pain intensity were significantly but weakly associated, and improvements in pain intensity score did not mediate improvements in insomnia score. Thus, improvements in self-reported insomnia in patients treated with SCS for chronic pain may predominantly be caused by other factors than reduced pain intensity.

Spinal Cord Stimulator Inequities Within the US Military Health System.

OBJECTIVES: Although studies have described inequities in spinal cord stimulation (SCS) receipt, there is a lack of information to inform system-level changes to support health care equity. This study evaluated whether Black patients exhaust more treatment options than do White patients, before receiving SCS. MATERIALS AND METHODS: This retrospective cohort study included claims data of Black and non-Latinx White patients who were active-duty service members or military retirees who received a persistent spinal pain syndrome (PSPS) diagnosis associated with back surgery within the US Military Health System, January 2017 to January 2020 (N = 8753). A generalized linear model examined predictors of SCS receipt within two years of diagnosis, including the interaction between race and number of pain-treatment types received. RESULTS: In the generalized linear model, Black patients (10.3% [8.7%, 12.0%]) were less likely to receive SCS than were White patients (13.6% [12.7%, 14.6%]) The interaction term was significant; White patients who received zero to three different types of treatments were more likely to receive SCS than were Black patients who received zero to three treatments, whereas Black and White patients who received >three treatments had similar likelihoods of receiving a SCS. CONCLUSIONS: In a health care system with intended universal access, White patients diagnosed with PSPS tried fewer treatment types before receiving SCS, whereas the number of treatment types tried was not significantly related to SCS receipt in Black patients. Overall, Black patients received SCS less often than did White patients. Findings indicate the need for structured referral pathways, provider evaluation on equity metrics, and top-down support.

Case report: Spinal cord stimulation for pain relief in two patients with locally recurrent pelvic malignancy.

Introduction: Chronic cancer-related pain from locally recurrent infiltrative cancers within the bony confines of the pelvis is a devastating and hard to manage condition that can be refractory to many conventional pain management methods. Spinal cord stimulation (SCS) is an evolving and safe method of pain management and can be trialled in a quick and well-tolerated operation under local anaesthesia. To date, this has not been reported in the setting of locally recurrent inoperable pelvic cancers. Case description: In the present study, we report two cases of patients with severe back and lower limb pain resulting from recurrent anal and rectal cancers involving the right lumbar and sacral nerve roots as well as the bony sacrum, which severely affected quality of life and daily functioning. Discussion: Following successful SCS, effective pain relief was observed. Conclusion: SCS could represent an effective supplementary or alternative technique to conventional pain management in this challenging group of patients, especially if other available methods have been exhausted.

Research hotspots and trends of spinal cord stimulation for neuropathic pain: a bibliometric analysis from 2004 to 2023.

The purpose of this study is to systematically analyze the development trend, research hotspots, and future development direction on the treatment of neuropathic pain (NP) with spinal cord stimulation through bibliometric method. We extracted the literature related to the treatment of NP with spinal cord stimulation from January 2004 to December 2023 from the Web of Science database. As a result, a total of 264 articles were retrieved. By analyzing the annual published articles, authors, countries, institutions, journals, co-cited literature, and keywords, we found that the count of publication in this field has been experiencing an overall growth, and the publications within the past 5 years accounted for 42% of the total output. Experts from the United States and the UK have made significant contributions in this field and established a stable collaborative team, initially establishing an international cooperation network. Pain is the frequently cited journal in this field. The study on spinal cord stimulation therapy for NP especially the study on spinal cord stimulation therapy for back surgery failure syndrome (FBSS) and its potential mechanisms are the research hotspots in this field, while the study on novel paradigms such as high-frequency spinal cord stimulation and spinal cord burst stimulation represents the future development directions. In short, spinal cord stimulation has been an effective treatment method for NP. The novel paradigms of spinal cord stimulation are the key point of future research in this field.

Electrical Stimulation and Motor Function Rehabilitation in Spinal Cord Injury: A Systematic Review.

Spinal cord injury (SCI) often leads to devastating motor impairments, significantly affecting the quality of life of affected individuals. Over the last decades, spinal cord electrical stimulation seems to have encouraging effects on the motor recovery of impacted patients. This review aimed to identify clinical trials focused on motor function recovery through the application of epidural electrical stimulation, transcutaneous electrical stimulation, and functional electrical stimulation. Several clinical trials met these criteria, focusing on the impact of the aforementioned interventions on walking, standing, swimming, trunk stability, and upper extremity functionality, particularly grasp. After a thorough PubMed online database research, 37 clinical trials were included in this review, with a total of 192 patients. Many of them appeared to have an improvement in function, either clinically assessed or recorded through electromyography. This review outlines the various ways electrical stimulation techniques can aid in the motor recovery of SCI patients. It stresses the ongoing need for medical research to refine these techniques and ultimately enhance rehabilitation results in clinical settings.

Non-invasive Transcutaneous Spinal Cord Stimulation Programming Recommendations for the Treatment of Upper Extremity Impairment in Tetraplegia.

OBJECTIVES: This study analyzes the stimulation parameters implemented during two successful trials that used non-invasive transcutaneous spinal cord stimulation (tSCS) to effectively improve upper extremity function after chronic spinal cord injury (SCI). It proposes a framework to guide stimulation programming decisions for the successful translation of these techniques into the clinic. MATERIALS AND METHODS: Programming data from 60 participants who completed the Up-LIFT trial and from 17 participants who subsequently completed the LIFT Home trial were analyzed. All observations of stimulation amplitudes, frequencies, waveforms, and electrode configurations were examined. The incidence of adverse events and relatedness to stimulation parameters is reported. A comparison of parameter usage across the American Spinal Injury Association Impairment Scale (AIS) subgroups was conducted to evaluate stimulation strategies across participants with varying degrees of sensorimotor preservation. RESULTS: Active (cathodal) electrodes were typically placed between the C3/C4 and C6/C7 spinous processes. Most sessions featured return (anodal) electrodes positioned bilaterally over the anterior superior iliac spine, although clavicular placement was frequently used by 12 participants. Stimulation was delivered with a 10-kHz carrier frequency and typically a 30-Hz burst frequency. Biphasic waveforms were used in 83% of sessions. Average stimulation amplitudes were higher for biphasic waveforms. The AIS B subgroup required significantly higher amplitudes than did the AIS C and D subgroups. Device-related adverse events were infrequent, and not correlated with specific waveforms or amplitudes. Within the home setting, participants maintained their current amplitudes within 1% of the preset values. The suggested stimulation programming framework dictates the following hierarchical order of parameter adjustments: current amplitude, waveform type, active/return electrode positioning, and burst frequency, guided by clinical observations as required. CONCLUSIONS: This analysis summarizes effective stimulation parameters from the trials and provides a decision-making framework for clinical implementation of tSCS for upper extremity functional restoration after SCI. The parameters are aligned with existing literature and proved safe and well tolerated by participants.

Diabetic Neuropathy: A Guide to Pain Management.

PURPOSE OF REVIEW: Diabetic neuropathy is a common complication of diabetes mellitus (DM) and can affect up to 50% of DM patients during their lifetime. Patients typically present with numbness, tingling, pain, and loss of sensation in the extremities. Since there is no treatment targeting the underlying mechanism of neuropathy, strategies focus on preventative care and pain management. RECENT FINDINGS: Up to 69% of patients with diabetic neuropathy receive pharmacological treatment for neuropathic pain. The United States Food and Drug Administration (FDA) confirmed four drugs for painful diabetic neuropathy (PDN): pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch. Nonpharmacological treatments such as spinal cord stimulation (SCS) and transcutaneous electrical nerve stimulation (TENS) both show promise in reducing pain in DM patients. Despite the high burden associated with PDN, effective management remains challenging. This update covers the background and management of diabetic neuropathy, including its epidemiology, pathogenesis, preventative care, and current therapeutic strategies.

External Oblique Intercostal Plane Block: A Case Report and Review of Literature.

Chronic low back pain (CLBP) and post-laminectomy syndrome (PLS) can pose significant therapeutic challenges, often refractory to conservative management. We present a case of a 52-year-old male with refractory CLBP and PLS who underwent spinal cord stimulation (SCS) lead placement, and subsequently developed chronic right anterior chest wall and upper abdominal pain. Despite using SCS and opioid therapy, the pain persisted until an ultrasound-guided external oblique intercostal plane block (EOIPB) was administered, resulting in complete pain relief. This case highlights the efficacy of EOIPB in managing chronic post-surgical neuropathic pain, underscoring its potential as a valuable intervention in such cases.

Durability of Evoked Compound Action Potential (ECAP)-Controlled, Closed-Loop Spinal Cord Stimulation (SCS) in a Real-World European Chronic Pain Population.

INTRODUCTION: Closed-loop spinal cord stimulation (CL-SCS) is a recently introduced system that records evoked compound action potentials (ECAPs) from the spinal cord elicited by each stimulation pulse and uses this information to automatically adjust the stimulation strength in real time, known as ECAP-controlled SCS. This innovative system compensates for fluctuations in the distance between the epidural leads and the spinal cord by maintaining the neural response (ECAP) at a predetermined target level. This data collection study was designed to assess the performance of the first CL-SCS system in a real-world setting under normal conditions of use in multiple European centers. The study analyzes and presents clinical outcomes and electrophysiological and device data and compares these findings with those reported in earlier pre-market studies of the same system. METHODS: This prospective, multicenter, observational study was conducted in 13 European centers and aimed to gather electrophysiological and device data. The study focused on the real-world application of this system in treating chronic pain affecting the trunk and/or limbs, adhering to standard conditions of use. In addition to collecting and analyzing basic demographic information, the study presents data from the inaugural patient cohort permanently implanted at multiple European centers. RESULTS: A significant decrease in pain intensity was observed for overall back or leg pain scores (verbal numerical rating score [VNRS]) between baseline (mean ± standard error of the mean [SEM]; n = 135; 8.2 ± 0.1), 3 months (n = 93; 2.3 ± 0.2), 6 months (n = 82; 2.5 ± 0.3), and 12 months (n = 76; 2.5 ± 0.3). Comparison of overall pain relief (%) to the AVALON and EVOKE studies showed no significant differences at 3 and 12 months between the real-world data release (RWE; 71.3%; 69.6%) and the AVALON (71.2%; 73.6%) and EVOKE (78.1%; 76.7%) studies. Further investigation was undertaken to objectively characterize the physiological parameters of SCS therapy in this cohort using the metrics of percent time above ECAP threshold (%), dose ratio, and dose accuracy (µV), according to previously described methods. Results showed that a median of 90% (40.7-99.2) of stimuli were above the ECAP threshold, with a dose ratio of 1.3 (1.1-1.4) and dose accuracy of 4.4 µV (0.0-7.1), based on data from 236, 230, and 254 patients, respectively. Thus, across all three metrics, the majority of patients had objective therapy metrics corresponding to the highest levels of pain relief in previously reported studies (usage over threshold > 80%, dose ratio > 1.2, and error < 10 µV). CONCLUSIONS: In conclusion, this study provides valuable insights into the real-world application of the ECAP-controlled CL-SCS system, highlighting its potential for maintaining effective pain relief and objective neurophysiological therapy metrics at levels seen in randomized control trials, and potential for quantifying patient burden associated with SCS system use via patient-device interaction metrics. CLINICAL TRIAL REGISTRATION: In the Netherlands, the study is duly registered on the International Clinical Trials Registry Platform (Trial NL7889). In Germany, the study is duly registered as NCT05272137 and in the United Kingdom as ISCRTN27710516 and has been reviewed by the ethics committee in both countries.

Insights into the pathophysiology and response of persistent spinal pain syndrome type 2 to spinal cord stimulation: a human genome-wide association study.

BACKGROUND: Spinal cord stimulation (SCS) provides pain relief for some patients with persistent spinal pain syndrome type 2 (PSPS 2), but the precise mechanisms of action and prognostic factors for a favorable pain response remain obscure. This in vivo human genome-wide association study provides some pathophysiological clues. METHODS: We performed a high-density oligonucleotide microarray analysis of serum obtained from both PSPS 2 cases and pain-free controls who had undergone lower back spinal surgery at the study site. Using multivariate discriminant analysis, we tried to identify different expressions between mRNA transcripts from PSPS 2 patients relative to controls, SCS responders to non-responders, or SCS responders to themselves before starting SCS. Gene ontology enrichment analysis was used to identify the biological processes that best discriminate between the groups of clinical interest. RESULTS: Thirty PSPS 2 patients, of whom 23 responded to SCS, were evaluated together with 15 pain-free controls. We identified 11 significantly downregulated genes in serum of PSPS 2 patients compared with pain-free controls and two significantly downregulated genes once the SCS response became apparent. All were suggestive of enhanced inflammation, tissue repair mechanisms and proliferative responses among the former. We could not identify any gene differentiating patients who responded to SCS from those who did not respond. CONCLUSIONS: This study points out various biological processes that may underlie PSPS 2 pain and SCS therapeutic effects, including the modulation of neuroimmune response, inflammation and restorative processes.

Transcutaneous Electrical Spinal Cord Stimulation Increased Target-Specific Muscle Strength and Locomotion in Chronic Spinal Cord Injury.

BACKGROUND: The recovery of locomotion is greatly prioritized, and neuromodulation has been emerging as a promising approach in recent times. STUDY DESIGN: Single-subject research design. SETTINGS: A laboratory at The Hong Kong Polytechnic University. OBJECTIVES: To investigate the effects of augmenting activity-based therapy (ABT) to transcutaneous electrical spinal cord stimulation (TSCS) on enhancing specific lower limb muscle strength and improving locomotor ability in an individual with chronic incomplete spinal cord injury (iSCI). METHODS: An individual with iSCI underwent two phases of treatment, ABT alone followed by combined ABT+TSCS, each for a period of 10 weeks. The TSCS stimulated T10-T11 and T12-L1 segments with a frequency of 30 Hz at an intensity between 105 mA and 130 mA. Manual muscle testing, 6 min walk test (6MWT), and surface electromyography (EMG) responses of specific lower limb muscles were measured. Additionally, spasticity and sensorimotor examinations were conducted every two weeks, while pain tolerance was recorded after each treatment session. RESULTS: After the ABT+TSCS treatment, there was an increase in overall muscle strength grading (from 1.8 ± 0.3 to 2.2 ± 0.6 out of 5.0). The 6MWT showed a greater increase in walking distance (3.5 m to 10 m) after combined treatment than ABT alone. In addition, the EMG response of the anterior rectus femoris, biceps femoris, medial gastrocnemius, and tibialis anterior after ABT+TSCS increased more than after ABT alone. The spasticity grade was reduced (from 0.8 ± 0.7 to 0.5 ± 0.6) whereas the average lower limb motor score increased from 17 to 23 points. No adverse effects were reported. CONCLUSIONS: ABT+TSCS increased the target-specific lower limb muscle strength and walking ability more than ABT alone in an individual with chronic iSCI.

Selective Activation of the Spinal Cord with Epidural Electrical Stimulation.

Spinal cord epidural electrical stimulation (EES) has been successfully employed to treat chronic pain and to restore lost functions after spinal cord injury. Yet, the efficacy of this approach is largely challenged by the suboptimal spatial distribution of the electrode contacts across anatomical targets, limiting the spatial selectivity of stimulation. In this study, we exploited different ESS paradigms, designed as either Spatial-Selective Stimulation (SSES) or Orientation-Selective Epidural Stimulation (OSES), and compared them to Conventional Monopolar Epidural Stimulation (CMES). SSES, OSES, and CMES were delivered with a 3- or 4-contact electrode array. Amplitudes and latencies of the Spinally Evoked Motor Potentials (SEMPs) were evaluated with different EES modalities. The results demonstrate that the amplitudes of SEMPs in hindlimb muscles depend on the orientation of the electrical field and vary between stimulation modalities. These findings show that the electric field applied with SSES or OSES provides more selective control of amplitudes of the SEMPs as compared to CMES. We demonstrate that spinal cord epidural stimulation applied with SSES or OSES paradigms in the rodent model could be tailored to the functional spinal cord neuroanatomy and can be tuned to specific target fibers and their orientation, optimizing the effect of neuromodulation.