Spinal Cord Stimulation Treatment Research Articles

A novel CNN-based image segmentation pipeline for individualized feline spinal cord stimulation modeling.

Spinal cord stimulation (SCS) is a well-established treatment for the management of certain chronic pain conditions. More recently, it has also garnered attention as a means of modulating neural activity with the goal of restoring lost autonomic or sensory-motor function. Personalized modeling and treatment planning are critical aspects of safe and effective SCS [46, 60]. However, the generation of spine models at the required level of detail and accuracy requires time and labor intensive manual image segmentation by human experts. Hence, there is a need for maximally automated segmentation routines capable of producing high-quality anatomical models that can be used even in cases where available data is limited. To this end, we developed an automated image segmentation and model generation pipeline based on a novel Convolutional Neural Network (CNN) architecture trained on feline spinal cord magnetic resonance imaging (MRI) data. The pipeline includes steps for image preprocessing, data augmentation, transfer learning and cleanup. To assess the relative importance of each step in the pipeline and of our choice of CNN architecture, we systematically dropped steps or substituted architectures, quantifying the downstream effects in terms of tissue segmentation quality (Jaccard index and Hausdorff distance) and predicted nerve recruitment (estimated axonal depolarization). This leaveone-out analysis demonstrated that each pipeline step contributed a small but measurable increment to mean segmentation quality. Surprisingly, minor differences in segmentation accuracy translated to significant deviations (ranging between 4% and 13% for each pipeline step) in predicted nerve recruitment, highlighting the importance of careful workflow design. To our knowledge, this is the first analysis to also assess the downstream impact of segmentation quality differences on neurostimulation predictions. Furthermore, transfer learning techniques enhanced segmentation metric consistency and allowed generalization to a completely different spine region with minimal additional training data. This work helps pave the way towards fully automated, personalized SCS treatment planning in clinical settings.

Postsynaptic dorsal column pathway activation during spinal cord stimulation in patients with chronic pain.

Spinal cord stimulation (SCS) treatment for chronic pain relies on the activation of primary sensory fibres ascending to the brain in the dorsal columns. While the efficacy of SCS has been demonstrated, the precise mechanism of action and nature of the fibres activated by stimulation remain largely unexplored. Our investigation in humans with chronic neuropathic pain undergoing SCS therapy, found that post-synaptic dorsal column (PSDC) fibres can be activated synaptically by the primary afferents recruited by stimulation, and axonically by the stimulation pulses directly. Synaptic activation occurred in 9 of the 14 patients analysed and depended on the vertebral level of stimulation. A clear difference in conduction velocities between the primary afferents and the PSDC fibres were observed. Identification of PSDC fibre activation in humans emphasises the need for further investigation into the role they play in pain relief and the sensory response sensation (paraesthesia) experienced by patients undergoing SCS.

Perceptions of pain in aging females undergoing spinal cord stimulation.

Aim: Effects of age and sex on chronic pain outcomes following spinal cord stimulation (SCS) have not yet been assessed. Methods: We retrospectively reviewed 1year outcomes from a database of patients receiving thoracic SCS. Subjects were divided into four cohorts: pre-menopausal and post-menopausal females, and aged-matched males. Improvement using the numerical rating scale, Oswestry Disability Index (ODI), Beck's Depression Inventory (BDI), McGill Pain Questionnaire and Pain Catastrophizing Scale (PCS) was assessed. Results: Older females were notably different from males and females under 60 as they had greater improvements in ODI, BDI and PCS. Further, females ≥60 had greater improvement in PCS compared with males ≥60. Conclusion: Our findings suggest greater improvement with 1year SCS treatment in post-menopausal females, compared with age-matched males.

Abstract 17051: Oxytocin Receptor in the Spinal Neuraxial Modulation of Ventricular Excitability

Introduction: Cardiac sympathoexcitation is a major contributor to the pathogenesis of ventricular tachyarrhymias (VTs) during ischemia reperfusion (I/R) and chronic myocardial infarction (MI). Afferent network connections in the intermediolateral cell column (IML) and dorsal horn (DH) control sympathetic output to the heart. Our team reported spinal cord stimulation (SCS), decreased cardiac sympathoexcitation and reduced VTs during ischemia. Oxytocin (OXT) is a known neuromodulator; however, whether OXT signaling can modulate the cardiospinal neural network is unknown. Hypothesis: SCS neuromodulation is reducing sympathoexcitation and VTs through OXT signaling pathways. Methods: Two models of cardiac ischemia were used in Yorkshire domestic swine. In acute I/R, a suture was placed around the left anterior descending (LAD) coronary artery, after sternotomy. Chronic infarction (MI) was created by accessing the femoral with fluoroscopy guidance. Polystyrene microspheres (1ml) were injected via a 3mm angioplasty balloon catheter to the LAD. Animals then recovered post-MI for 6-8wk. SCS treatment was delivered through a four-pole lead which was inserted in the epidural space (T1-T4)(50Hz, 0.4ms pulse duration). T2-T4 spinal cord was collected postmortem for molecular analysis. Fluorescence in situ hybridization (FISH) protocol for RNAscope Fluorescent v2 Assay (ACD) was followed. Cell counts represented as 3 puncta or more centered around DAPI. Results: We report that OXT receptor positive cells significantly decreased as a result of I/R and MI (p<0.001, two-way ANOVA n=4-5 animals, average of 2-3 slices per animal). Within the DH the majority of OXT positive cells were inhibitory GABAergic neurons. Within the IML, a majority of the cells regulated by I/R and MI were microglia, and both an inhibitory and excitatory population contributed to the onset of ischemia. SCS treatment after I/R and MI resulted in the recovery of this OXT receptor cell population. Conclusions: By evaluating the role of OXT in reducing cardiac sympathoexcitation at the level of the spinal cord, we provide new insights into optimizing current neuromodulation approaches and developing new pharmacologic therapies.

Comparison Between the Efficacy of Spinal Cord Stimulation and of Endovascular Revascularization in the Treatment of Diabetic Foot Ulcers: A Retrospective Observational Study

ObjectiveWe aimed to compare the effects of spinal cord stimulation (SCS) with those of endovascular revascularization on the treatment of diabetic foot ulcers. Materials and MethodsA total of 104 patients with diabetic foot ulcers who met the inclusion criteria were retrospectively analyzed and classified to the SCS treatment group (n = 46) and endovascular revascularization treatment group (n = 46). The quality-of-life scores (Quality of Life Scale for Patients with Liver Cancer v2.0), visual pain analog scale score, lower limb skin temperature, lower limb arterial ultrasound results, and lower extremity electromyography results were analyzed to compare the efficacy of the two treatments for diabetic foot ulcers in the two groups before surgery and six months after surgery. ResultsA total of 92 patients (men: 73.9%, mean age: 66.51 ± 11.67 years) completed the six-month postoperative follow-up period. The patients in the SCS treatment group had a higher quality-of-life score (25.54% vs 13.77%, p < 0.05), a larger reduction in pain scores (69.18% vs 37.21%, p < 0.05), and a larger reduction in foot temperature (18.56% vs 7.24%, p < 0.05) than those of the endovascular revascularization treatment group at six months after surgery. The degree of vasodilation in the lower limbs on color Doppler arterial ultrasound and the nerve conduction velocity were higher in the SCS treatment group than in the endovascular revascularization treatment group at six months after surgery (p < 0.05). ConclusionSCS was more effective than endovascular revascularization in improving quality of life, relieving pain, improving lower limb skin temperature, increasing lower limb blood flow, and improving nerve conduction in patients with diabetic foot ulcers at six months after surgery.

Objective wearable measures correlate with self-reported chronic pain levels in people with spinal cord stimulation systems

Spinal Cord Stimulation (SCS) is a well-established therapy for treating chronic pain. However, perceived treatment response to SCS therapy may vary among people with chronic pain due to diverse needs and backgrounds. Patient Reported Outcomes (PROs) from standard survey questions do not provide the full picture of what has happened to a patient since their last visit, and digital PROs require patients to visit an app or otherwise regularly engage with software. This study aims to assess the feasibility of using digital biomarkers collected from wearables during SCS treatment to predict pain and PRO outcomes. Twenty participants with chronic pain were recruited and implanted with SCS. During the six months of the study, activity and physiological metrics were collected and data from 15 participants was used to develop a machine learning pipeline to objectively predict pain levels and categories of PRO measures. The model reached an accuracy of 0.768 ± 0.012 in predicting the pain intensity of mild, moderate, and severe. Feature importance analysis showed that digital biomarkers from the smartwatch such as heart rate, heart rate variability, step count, and stand time can contribute to modeling different aspects of pain. The results of the study suggest that wearable biomarkers can be used to predict therapy outcomes in people with chronic pain, enabling continuous, real-time monitoring of patients during the use of implanted therapies.

1809-PUB: Painful Diabetic Neuropathy—Patients Treated with High-Frequency (10 kHz) Spinal Cord Stimulation (SCS) Experience Significant Reductions in A1C and Weight

Objective: Up to 9 million Americans have painful diabetic neuropathy (PDN), which can be debilitating. For PDN patients, 10 kHz SCS has been shown to provide mean pain relief of 77% at 24 months (24M), and here we report secondary, novel potential benefits for A1C and body weight. Methods: Subjects received a 10 kHz SCS implant plus medical management for their pain and diabetes. Subjects were followed for 24M post-implantation. Key inclusion criteria were: PDN ≥12M refractory to medications, lower limb pain ≥5cm (10cm VAS), and A1C ≤10%. For T2D subjects, changes in weight were evaluated for all subjects and cohorts with pre-implant BMI ≥30 and ≥35, and changes in A1C were evaluated for cohorts with pre-implant A1C ≥7.0% and ≥8.0%. Results: For cohorts evaluated, A1C and weight generally decreased with time (Fig. 1). For subjects with pre-implant A1C ≥8.0%, the mean A1C reduction was 0.52% at 6M (p=0.064) and 1.04% at 24M (p=0.007). For all subjects, the mean weight reduction was 1.8 kg at 12M (p=0.058) and 3.1 kg at 24M (p=0.003). For subjects with pre-implant BMI ≥35, the mean weight reduction was 5.4 kg at 24M (p=0.005). Conclusions: Previously reported pain relief and sensory improvement, coupled with reductions in A1C and weight reported here, further demonstrate the benefits of 10 kHz SCS treatment in the comprehensive care of T2D patients with PDN. Disclosure D.C.Klonoff: Consultant; EOFlow Co., Ltd., Fractyl Health, Inc., Integrity, Lifecare, Inc., Rockley Photonics, Thirdwayv Inc. B.L.Levy: Advisory Panel; Nevro Corp., CeQur SA, Consultant; Nevro Corp., CeQur SA, Digma Medical. M.Jaasma: Consultant; Bone Health Technologies, Inc., Employee; Nevro Corp., Bone Health Technologies, Inc. M.Bharara: Employee; Nevro Corp. C.E.Nasr: Advisory Panel; Siemens, Horizon Therapeutics plc. D.L.Caraway: Employee; Nevro Corp. E.Petersen: Consultant; Abbott, Biotronik, Medtronic, Nalu, Nevro Corp., Presidio Medical, Saluda Medical, Vertos Medical Inc., Research Support; Nalu, Nevro Corp. D.G.Armstrong: Research Support; Medaxis LLC. Funding Nevro Corp.

ID: 219132 Variables Associated With Non-Responders to 10kHz Spinal Cord Stimulation: A Retrospective Review of Preliminary Data

Non-response to 10kHz spinal cord stimulation (SCS) treatment has been documented in the literature as less than 50% subjective improvement in pain at 3-months post-implant1-5. Appropriateness in selection criteria is one of the most important factors associated with successful outcomes, but limited literature reports predictive factors in non-responders. Therefore, we aim to identify such variables and help distinguish the subset less likely to benefit from SCS.

ID: 199756 Improving Access to SCS Care and Treatment Efficiency Using Patient and Clinician Digital-Applications

Recent data has shown high patient engagement and improved trial outcomes in Spinal Cord Stimulation (SCS) by utilizing a novel real-time tracking application.1 Such digital applications (apps) and tools have gained considerable interest from both patients and providers alike for their potential to improve access to care, efficient delivery of therapy, and engagement during treatment. A suite of digital tools has been developed that allow for identification of bottlenecks in patient care, increased throughput of pre-authorization processes, enhanced patient engagement during the trial, and clinic-specific insights into the efficiency of care delivery for SCS patients. These new technologies offer key support to SCS-implanting centers and providers to address the inefficiencies and hurdles that restrict patient access to therapy. Here, we describe our initial appraisal of a collection of newly available digital health tools for use in the real-world clinical and/or other remote settings.

Painful Peripheral Neuropathies of the Lower Limbs and/or Lower Extremities Treated with Spinal Cord Stimulation: A Systematic Review with Narrative Synthesis.

Painful peripheral neuropathy (PPN) is a debilitating condition with varied etiologies. Spinal cord stimulation (SCS) is increasingly used when conservative treatments fail to provide adequate pain relief. Few published reviews have examined SCS outcomes in all forms of PPN. We conducted a systematic review of SCS in PPN. The PubMed database was searched up to February 7th, 2022, for peer-reviewed studies of SCS that enrolled PPN patients with pain symptoms in their lower limbs and/or lower extremities. We assessed the quality of randomized controlled trial (RCT) evidence using the Cochrane risk of bias tool. Data were tabulated and presented narratively. Twenty eligible studies documented SCS treatment in PPN patients, including 10 kHz SCS, traditional low-frequency SCS (t-SCS), dorsal root ganglion stimulation (DRGS), and burst SCS. In total, 451 patients received a permanent implant (10 kHz SCS, n=267; t-SCS, n=147; DRGS, n=25; burst SCS, n=12). Approximately 88% of implanted patients had painful diabetic neuropathy (PDN). Overall, we found clinically meaningful pain relief (≥30%) with all SCS modalities. Among the studies, RCTs supported the use of 10 kHz SCS and t-SCS to treat PDN, with 10 kHz SCS providing a higher reduction in pain (76%) than t-SCS (38-55%). Pain relief with 10 kHz SCS and DRGS in other PPN etiologies ranged from 42-81%. In addition, 66-71% of PDN patients and 38% of nondiabetic PPN patients experienced neurological improvement with 10 kHz SCS. Our review found clinically meaningful pain relief in PPN patients after SCS treatment. RCT evidence supported the use of 10 kHz SCS and t-SCS in the diabetic neuropathy subpopulation, with more robust pain relief evident with 10 kHz SCS. Outcomes in other PPN etiologies were also promising for 10 kHz SCS. In addition, a majority of PDN patients experienced neurological improvement with 10 kHz SCS, as did a notable subset of nondiabetic PPN patients.

Abstract #1399039: Treatment of Painful Diabetic Neuropathy: 10 kHz SCS Provides Durable Pain Relief and Sensory Improvements

Of the 37 million Americans who have diabetes, up to 25% experience painful diabetic neuropathy (PDN). While conventional medical management (CMM), which includes pharmacotherapies, can be ineffective for many patients, high-frequency (10 kHz) spinal cord stimulation (SCS) has been shown to provide substantial symptom relief for PDN. Here we report durability of outcomes to 24 months (24M) months for 10 kHz SCS treatment of PDN. We conducted a prospective, multicenter, randomized, controlled trial (RCT) to evaluate 10 kHz SCS in PDN patients. Key inclusion criteria were: PDN symptoms ≥12M refractory to medications, lower limb pain intensity ≥5cm (0-10cm visual analog scale [VAS]), and hemoglobin A1c ≤10%. Patients (n=216) were randomized 1:1 to 10 kHz SCS plus CMM or CMM alone, with optional treatment group crossover at 6M. Patients randomized to 10 kHz SCS experienced average pain relief of 76% at 6M, while patients receiving CMM alone experienced average pain increase of 2%. After 6M, 93% of eligible CMM patients crossed over to 10 kHz SCS, while no 10 kHz SCS patients crossed over to CMM. At 24M, patients receiving 10 kHz SCS experienced durable pain relief, with average pain relief of 80%. Reductions in pain-associated sleep disturbance and pain interference with mood and daily activities were consistent with pain relief. At 6M, 10 kHz SCS provided substantial reductions vs. CMM. At 24M, patients receiving 10 kHz SCS experienced a 65% decrease in pain-associated sleep disturbance and a 67% decrease in pain interference with mood and daily activities. Clinician-assessed sensory function improvements in the feet and legs were observed with 10 kHz SCS. At 6M, improvements were observed in 59% of patients receiving 10 kHz SCS vs. only 9% of patients receiving CMM alone. Sensory improvements were durable as 65% of patients receiving 10 kHz SCS had improvements at 24M. In total, 154 patients received an SCS implant. There were eight (5.2%) study-related infections (n=3 resolved; n=5 (3.2%) explanted), which is within the range reported across all SCS patient populations (2.5-10%). The results of this RCT demonstrate that 10 kHz SCS provides durable reductions in pain and pain-associated effects on health-related quality of life with acceptable safety, now observed through 24-month follow-up. The durable sensory function improvements highlight the disease-modifying potential of 10 kHz SCS.

10 kHz SCS Provides Durable Pain Relief and Neurological Improvements for Patients with Painful Diabetic Neuropathy: 24-Month RCT Results (PL4.004)

10 kHz SCS Provides Durable Pain Relief and Neurological Improvements for Patients with Painful Diabetic Neuropathy: 24-Month RCT Results (PL4.004)

Effect of stimulation intensity of a differential target multiplexed SCS program in an animal model of neuropathic pain.

Spinal cord stimulation (SCS) has been proven to be an effective treatment for patients suffering from intractable chronic neuropathic pain. Recent advances in the field include the utilization of programs that multiplex various signals to target different neural structures in the dorsal spinal cord associated with the painful area. Preclinical studies have been fundamental in understanding the mechanism by which this differential target multiplexed programming (DTMP) SCS approach works. Transcriptomic- and proteomic-based studies demonstrated that DTMP can modulate expression levels of genes and proteins involved in pain-related processes that have been affected by a neuropathic pain model. This work studied the effect of the intensity of DTMP signals on mechanical hypersensitivity and cell-specific transcriptomes. The spared nerve injury model (SNI) of neuropathic pain was induced in 20 animals which were 1:1 randomized into two SCS groups in which the intensity of the DTMP was adjusted to either 70% or 40% of the motor threshold (MT). SCS was applied continuously for 48 h via a quadripolar lead implanted in the dorsal epidural space of animals. Controls, which included a group of implanted SNI animals that received no SCS and a group of animals naive to the SNI, were assessed in parallel to the SCS groups. Mechanical hypersensitivity was assessed before SNI, before SCS, and at 48 h of SCS. At the end of SCS, the stimulated segment of the dorsal spinal cord was dissected and subjected to RNA sequencing to quantify expression levels in all experimental groups. Differential effects were assessed via fold-change comparisons of SCS and naive groups versus the no-SCS group for transcriptomes specific to neurons and glial cells. Standard statistical analyses were employed to assess significance of the comparisons (p < 0.05). SCS treatments provided significant improvement in mechanical sensitivity relative to no SCS treatment. However, the change in the intensity did not provide a significant difference in the improvement of mechanical sensitivity. DTMP regulated expression levels back toward those found in the naive group in the cell-specific transcriptomes analyzed. There were no significant differences related to the intensity of the stimulation in terms of the percentage of genes in each transcriptome in which expression levels were reversed toward the naive state. DTMP when applied at either 40% MT or 70% MT provided similar reduction of pain-like behavior in rats and similar effects in neuron- and glia-specific transcriptomes.

The Effectiveness of Various Types of Electrical Stimulation of the Spinal Cord for Chronic Pain in Patients with Postherpetic Neuralgia: A Literature Review.

Postherpetic neuralgia (PHN) is a severe condition that remains a challenge to treat. Spinal cord stimulation (SCS) is used in cases of insufficient efficacy of conservative treatment. However, in contrast to many other neuropathic pain syndromes, there is a huge problem in reaching long-term stable pain relief in patients with PHN using conventional tonic SCS. The objective of this article was to present a review of the current management strategies of PHN, their efficacy, and safety. We searched for articles containing the keywords "spinal cord stimulation AND postherpetic neuralgia," "high-frequency stimulation AND postherpetic neuralgia," "burst stimulation AND postherpetic neuralgia" and "dorsal root ganglion stimulation AND postherpetic neuralgia" in Pubmed, Web of Science, and Scopus databases. The search was limited to human studies published in the English language. There were no publication period limitations. Bibliographies and references of selected publications on neurostimulation for PHN were further manually screened. The full text of each article was studied once the abstract was analyzed by the searching reviewer and found appropriate. The initial search yielded 115 articles. Initial screening based on abstract and title allowed us to exclude 29 articles (letters, editorials, and conference abstracts). The full-text analysis allowed us to exclude another 74 articles (fundamental research articles, research utilizing animal subjects, and systemic and nonsystemic reviews) and results of PHN treatment presented with other conditions, leaving 12 articles for the final bibliography. 12 articles reporting on the treatment of 134 patients with PHN were analyzed, with a disproportionally large amount of traditional SCS treatment than that to alternative SCS: DRGS (13 patients), burst SCS (1 patient), and high-frequency SCS (2 patients). Long-term pain relief was achieved in 91 patients (67.9%). The mean VAS score improvement was 61.4% with a mean follow-up time of 12.85 months. Although the number of patients in alternative SCS studies was very limited, almost all of them showed good responses to therapy with more than 50% VAS improvement and reduction of analgesic dosage. The article contains a review analysis of 12 articles concerning the current methods of treatment for postherpetic neuralgia including conservative treatment, spinal cord stimulation, and novel neuromodulation strategies. Available information on the pathophysiology of PHN and the effect or stimulation on its course, together with a number of technical nuances concerning various types of neurostimulation are also elucidated in this article. A number of alternative invasive treatments of PHN are also discussed. Spinal cord stimulation is an established treatment option for patients with pharmacologically resistant PHN. High-frequency stimulation, burst stimulation, and dorsal root ganglion stimulation are promising options in the management of PHN due to the absence of paresthesias which can be painful for patients with PHN. But more research is still required to recommend the widespread use of these new methods.

Heterogeneous Cortical Effects of Spinal Cord Stimulation

ObjectivesThe understanding of the cortical effects of spinal cord stimulation (SCS) remains limited. Multiple studies have investigated the effects of SCS in resting-state electroencephalography. However, owing to the large variation in reported outcomes, we aimed to describe the differential cortical responses between two types of SCS and between responders and nonresponders using magnetoencephalography (MEG). Materials and MethodsWe conducted 5-minute resting-state MEG recordings in 25 patients with chronic pain with active SCS in three sessions, each after a one-week exposure to tonic, burst, or sham SCS. We extracted six spectral features from the measured neurophysiological signals: the alpha peak frequency; alpha power ratio (power 7–9 Hz/power 9–11 Hz); and average power in the theta (4–7.5 Hz), alpha (8–12.5 Hz), beta (13–30 Hz), and low-gamma (30.5–60 Hz) frequency bands. We compared these features (using nonparametric permutation t-tests) for MEG sensor and cortical map effects across stimulation paradigms, between participants who reported low (< 5, responders) vs high (≥ 5, nonresponders) pain scores, and in three representative participants. ResultsWe found statistically significant (p < 0.05, false discovery rate corrected) increased MEG sensor signal power below 3 Hz in response to burst SCS compared with tonic and sham SCS. We did not find statistically significant differences (all p > 0.05) between the power spectra of responders and nonresponders. Our data did not show statistically significant differences in the spectral features of interest among the three stimulation paradigms or between responders and nonresponders. These results were confirmed by the MEG cortical maps. However, we did identify certain trends in the MEG source maps for all comparisons and several features, with substantial variation across participants. ConclusionsThe considerable variation in cortical responses to the various SCS treatment options necessitates studies with sample sizes larger than commonly reported in the field and more personalized treatment plans. Studies with a finer stratification between responders and nonresponders are required to advance the knowledge on SCS treatment effects.

Potential benefits of spinal cord stimulation treatment on quality of life for paralyzed patients with spinal cord injury.

Spinal cord injury (SCI) is a severe central nervous system injury that can cause sensory or motor dysfunction. Although mortality rates for people with spinal cord injuries have dropped dramatically with advances in medicine, chronic long-term sequelae after SCI persist. The most bothersome problems reported by patients include pain, spasticity, urinary dysfunction, and loss of motor function. Thus, quality of life (QoL) is an essential issue in chronic SCI. Spinal cord stimulation (SCS) applies an adjustable, nondamaging electrical pulse that can reduce uncomfortable comorbidities and improve mobility, thus enhancing the QoL of patients with SCI. This review summarizes pivotal breakthroughs from SCS for individual clinical impairment from SCI. We conclude that careful evaluation of SCS can help improve neuropathic pain, spasms, motor symptoms, and voiding dysfunction in patients with SCI, thus improving QoL.

Real World Clinical Utility of Neurophysiological Measurement Utilizing Closed-Loop Spinal Cord Stimulation in a Chronic Pain Population: The ECAP Study Protocol.

Spinal cord stimulation (SCS) is an established chronic pain treatment, but the effectiveness of traditional, open-loop paradigms has been plagued by variable sustainability in a real-world setting. A new approach, utilizing evoked compound action potential (ECAP) controlled closed-loop (CL) SCS, continuously monitors spinal cord activation and automatically adjusts the stimulation amplitude of every pulse, maintaining stimulation at the prescribed ECAP level through this continual feedback mechanism. Recent studies demonstrated the long-term safety and efficacy of ECAP-controlled CL-SCS. Here, we report the design of a prospective, multicenter, single-arm feasibility study to characterize clinical outcomes in a real-world chronic pain population utilizing ECAP-controlled CL-SCS. Objective neurophysiological measurements such as device performance and patient therapy compliance, will be analyzed against baseline biopsychosocial assessments, to explore the clinical utility of these objective physiologic biomarkers in patient phenotyping. This study will enroll up to 300 subjects with chronic, intractable trunk and/or limb pain in up to 25 United States investigation sites. Subjects meeting eligibility criteria will undergo a trial procedure and a permanent implant following a successful trial. Neurophysiological measurements (measured in-clinic and continuously during home use) and clinical outcomes including pain, quality-of-life, psychological, emotional, and functional assessments will be collected at baseline, trial end, and up to 24-months post-implantation. Associations between objective neurophysiological data, clinical evaluation and patient-reported outcomes may have important clinical and scientific implications. They may provide novel insights about the chronic pain pathophysiology, its modulation during CL-SCS, and identification of pain phenotypes and/or mechanisms associated with treatment response during SCS trials and long-term therapy. Data from the ECAP study could lead to improvements in diagnosis, assessment, patient identification and management of chronic pain. It could also provide the foundation for development of a new SCS treatment approach customized by the patient's pain phenotype, unique neurophysiology, and disease severity.

Long-Term Evaluation of Spinal Cord Stimulation in Patients With Painful Diabetic Polyneuropathy: An Eight-to-Ten–Year Prospective Cohort Study

ObjectiveThis study aimed to evaluate the long-term effects of spinal cord stimulation (SCS) in patients with painful diabetic polyneuropathy (PDPN). Materials and MethodsThis prospective cohort study was the eight-to-ten–year follow-up of a previously performed pilot and randomized controlled trial on the effects of SCS in PDPN, initiated by the multidisciplinary pain center of Maastricht University Medical Center+. The study population consisted of a subgroup of patients who still used SCS treatment ≥ eight years after implantation (n = 19). Pain intensity scores (numeric rating scale [NRS]) during the day and night and data on secondary outcomes (ie, quality of life, depression, sleep quality) were reported during yearly follow-up consultations. Long-term efficacy of SCS was analyzed by comparing the most recently obtained data eight to ten years after implantation with those obtained at baseline. ResultsPain intensity, day and night, was significantly (p < 0.01) reduced by 2.3 (NRS 6.6–4.3) and 2.2 (NRS 6.8–4.6) points, respectively, when comparing the long-term data with baseline. Moreover, for > 50% of patients, the pain reduction was > 30%, which is considered clinically meaningful. No differences were found regarding the secondary outcomes. ConclusionThis eight-to-ten–year follow-up study indicates that SCS can remain an effective treatment in the long term to reduce pain intensity in a subcohort of patients with PDPN who still had an SCS device implanted after eight years.

Elevated cerebrospinal fluid protein levels associated with poor short-term outcomes after spinal cord stimulation in patients with disorders of consciousness.

Spinal cord stimulation (SCS) is a promising treatment for patients with disorders of consciousness (DoC); however, the laboratory examinations and different electrodes (permanent #39286 vs. temporary percutaneous #3777, Medtronic, USA) that are associated with postoperative outcomes are unclear. The study aims to study the association between the change in postoperative cerebrospinal fluid (CSF) protein level and improvement in consciousness after SCS in DoC patients and to explore whether different electrodes were associated with elevated CSF protein levels. A total of 66 DoC patients who received SCS treatment from December 2019 to December 2021 were retrospectively analyzed. Patients were grouped according to their elevated CSF protein level. The clinical characteristics of the patients and SCS stimulation parameters were compared. The preoperative sagittal diameter of the spinal canal is the distance from the midpoint of the posterior border of the vertebral body to the midpoint of the posterior wall of the spinal canal at the level of the superior border of C3. The postoperative sagittal diameter of the spinal canal is the distance from the midpoint of the posterior edge of the vertebral body to the anterior edge of the stimulation electrode. Patients with improved postoperative CRS-R scores greater than 3 or who progressed to the MCS + /eMCS were classified as the improved group and otherwise regarded as poor outcome. We found that more DoC patients had elevated CSF protein levels among those receiving SCS treatment with permanent electrodes than temporary percutaneous electrodes (P = 0.001), and elevated CSF protein levels were significantly associated with a reduced sagittal diameter (P = 0.044). In DoC patients receiving SCS treatment, we found that elevated CSF protein levels (P = 0.022) and preoperative diagnosis (P = 0.003) were significantly associated with poor outcomes at 3 months. Logistic regression analysis showed that elevated CSF protein levels were significantly associated with poor outcomes (OR 1.008, 95% CI 1.001-1.016, P = 0.032). The results suggest that reducing the effect of electrode pads on anatomical changes may help improve the outcomes of DoC patients receiving SCS treatment. CSF protein levels are associated with poor postoperative outcomes and whether they are potential biomarkers in DoC patients receiving SCS treatment remain further exploration.

Short-term spinal cord stimulation in treating disorders of consciousness monitored by resting-state fMRI and qEEG: The first case report

Disorders of consciousness (DOC) are one of the most frequent complications in patients after severe brain injury, mainly caused by trauma, stroke, and anoxia. With the development of neuromodulation techniques, novel therapies including deep brain stimulation (DBS) and spinal cord stimulation (SCS) have been employed to treat DOC. Here, we report the case of a DOC patient receiving short-term SCS (st-SCS) treatment and showing improvement monitored by resting-state fMRI (rs-fMRI) and quantitative EEG (qEEG). A 35-year-old male with severe traumatic brain injury remained comatose for 3 months. The patient was evaluated using JFK coma recovery scale-revised (CRS-R) and showed no improvement within 1 month. He received st-SCS surgery 93 days after the injury and the stimulation was applied the day after surgery. He regained communication according to instructions on day 21 after surgery and improved from a vegetative state/unwakefulness syndrome to an emergence from a minimally conscious state. To our knowledge, this report is the first published case of st-SCS in a patient with DOC. These results shed light that st-SCS may be effective in treating certain patients with DOC, which may reduce patients' suffering during treatment and lessen financial burden.