Search Results (133)

Spinal cord stimulation (SCS) is a widely used neuromodulatory therapy for chronic neuropathic pain, yet the cellular and molecular mechanisms underlying its clinical efficacy remain incompletely understood. This review synthesizes current literature on the neurophysiology of pain transmission and the mechanistic basis of major SCS paradigms (tonic, high-frequency, burst, and closed-loop stimulation), highlighting how each modality engages distinct dorsal horn circuits, glial and inflammatory pathways, as well as supraspinal networks involved in the affective dimension of pain. Particular attention is given to the evoked compound action potential (ECAP) as an emerging electrophysiological biomarker that enables real-time, feedback-guided stimulation and offers insight into the biophysical determinants of dorsal column activation. We also examine preclinical and clinical evidence linking SCS to modulation of central sensitization, neuroinflammatory signaling, and autonomic regulation, while identifying persistent gaps in mechanistic understanding. Finally, we discuss future directions, including AI-assisted, personalized SCS programming and expanding indications beyond classical neuropathic pain, underscoring the need for multimodal experimental approaches to more precisely define how SCS achieves analgesia. Full article

Background/Objectives: Spinal cord epidural stimulation (scES) holds significant potential for restoring autonomic function after chronic spinal cord injury (SCI). A significant and often debilitating sequela of SCI is neurogenic lower urinary tract dysfunction, characterized by loss of voluntary bladder control, which adversely impacts patients’ dignity, urological health, and overall quality of life. In a pilot study of three individuals with SCI, an epidural electrode array was implanted between L2 and sacral segments to modulate lower urinary tract function for efficient emptying. Methods: Three participants with chronic thoracic clinically complete SCI were implanted with an epidural stimulator over the lumbosacral spinal cord. Array placement was confirmed using intraoperative and postoperative spatiotemporal mapping of known motor neuron pools following published protocols. In a controlled laboratory mapping, bladder storage and voiding neural networks were targeted during filling cystometry by interactively optimizing lower urinary tract stimulation parameters (electrode configuration, frequency, intensity, and pulse width). Efficacy was assessed during six-hour laboratory sessions of natural bladder filling, followed by approximately four months of daily at-home use. Results: Pre-implant cystometry revealed poor voiding efficiency and absent bladder sensation. Following bladder scES mapping and home training, one of the three participants regained direct bladder sensation, exceeded the 90% clinical threshold for efficient voiding, and continues to use scES for bladder management instead of intermittent catheterization, with no urinary tract infections reported since completion of training (February 2022). The inability of two participants to attain high voiding efficiency may be due to suboptimal adherence to prescribed bladder training protocols in one case and the presence of an elevated bladder neck in the other. All three participants reported off-target improvements in bowel and sexual functions. Conclusions: The present novel pilot study provides the first evidence supporting the potential use of epidural stimulation for bladder management and the importance of activity-based recovery training for durable performance. Full article

Background/Objectives: The mandatory spinal cord stimulation (SCS) trial was established in the era of tonic, paresthesia-dependent stimulation, when pre-implantation outcome prediction was unreliable, validated psychological screening was unavailable, and post-implantation programming options were limited. This narrative review examines whether universal trialing remains justified in the context of contemporary paresthesia-free waveforms, mechanistically informed psychological assessment, and current evidence on the predictive utility of screening trials. The objective was to evaluate the contemporary rationale for selective rather than universal trialing and to propose a structured four-step clinical decision framework integrating contraindication screening, pain phenotype certainty, psychological risk stratification, and centre-level criteria, with the aim of identifying patients in whom a trial is most likely to add prognostic information. Methods: PubMed and the Cochrane Library were searched using predefined search strings. Eligible publications included randomised controlled trials (including the TRIAL-STIM RCT), systematic reviews, registry-based cohort studies, health-economic analyses, and consensus guidelines. Results: The evidence base comprised randomised controlled trials of trial-versus-no-trial strategies, paresthesia-free waveforms, and closed-loop stimulation (including TRIAL-STIM, SENZA-RCT, EVOKE, and ECHO-MAC), together with large registry and cohort studies, systematic reviews, qualitative patient-experience data, and current consensus guidance. Modern paresthesia-free and physiology-guided paradigms reduce several technical functions historically served by trialing, although the extent varies by waveform. The only randomised trial designed specifically to compare trial-first and no-trial strategies (TRIAL-STIM) found no difference in pain outcomes at 6 or 36 months; however, its single healthcare setting and predominantly paresthesia-based waveform mix limit generalisability. Structured pre-implantation psychological evaluation may provide prognostic information that short-duration trialing cannot replicate. At the same time, contemporary guidelines continue to recommend trialing and several clinically relevant arguments for retaining it persist, including patient experiential learning, identification of screening false negatives, and grey-zone decision-making. Conclusions: In carefully selected patients with established neuropathic pain phenotypes and comprehensive pre-implantation evaluation, selective trialing may be clinically reasonable. The proposed four-step framework offers a structured basis for allocating trial stimulation to the patients most likely to benefit from it and should be interpreted as hypothesis-generating pending prospective validation. This review does not advocate abandoning trial stimulation; rather, it argues that its role should be examined within an individualised, phenotype- and risk-stratified pathway. Full article

Background: Neuromuscular deficits may persist following anterior cruciate ligament reconstruction (ACLR), even after returning to sport. In this exploratory case series, we investigated the effects of non-invasive spinal cord transcutaneous stimulation (scTS), applied during warm-up for approximately 25 min to prime the nervous system, on neuromuscular performance of the ACLR limb during a simulated half-squat power training session. Methods: Four young, non-professional athletes with time since ACLR between 9.0 and 14.5 months, who were already returned to sport, participated in this study. Force, velocity, power, and electromyography of representative thigh muscles generated by the ACLR and intact limbs during unilateral half-squats on a Smith machine, were assessed over two separate experimental sessions (scTS or sham stimulation priming). Results: Three of the four participants showed power deficit in the ACLR limb during the concentric phase. scTS priming promoted higher power output generated by the ACLR limb in these three participants. Oscillatory-like force pattern during the downward phase was more prominent in the ACLR limb for one subject, and scTS priming attenuated it. Conclusions: These findings support future controlled trials to assess the efficacy of scTS priming as an aid to enhance rehabilitation and physical training after ACLR. Full article

Background/Objectives: Spinal cord stimulation (SCS) is usually evaluated through pain relief, yet the published language of therapeutic success is broader. This structured narrative review examined success language in the SCS literature to map how outcome terminology has accumulated across domains. Methods: A PubMed/MEDLINE corpus was retrieved on 23 May 2026 using the strategy (“Spinal Cord Stimulation”[Mesh] OR “Spinal Cord Stimulation”[Title/Abstract]). The search returned 5719 records from 1961 to 2026. Title-and-abstract screening was performed independently by two authors, with pre-consensus agreement of 99.77% (Cohen’s κ = 0.995). After screening, 3687 records were retained for thematic narrative synthesis. Results: Pain relief or analgesic response appeared in 3550 retained records (96.3%) and remained the dominant outcome language across decades. Additional domains accumulated around it: function, quality of life, and sleep (72.5%); durability (55.5%); complications and device burden (51.0%); trial stimulation (44.1%); patient selection (40.5%); paresthesia coverage (29.9%); patient preference (24.5%); economic or occupational outcomes (22.8%); stimulation paradigm (21.9%); and medication use (21.3%). Physiological-feedback language was separated into mechanism-related language, objective monitoring, and evoked compound action potential (ECAP)-controlled closed-loop feedback. Conclusions: Within this corpus, SCS success emerged as a layered concept: analgesia remained central but was increasingly reported alongside other outcome domains rather than standing as the sole reported marker of therapeutic success. Importantly, this review maps the published language of outcome reporting, not clinical practice, payer behaviour, or any formal redefinition of treatment success; the findings should not be read as evidence that SCS success is now uniformly defined in multidimensional terms, and this scope is essential when interpreting the findings. Full article

Transcutaneous spinal cord stimulation (tSCS) is a promising neuromodulation approach for motor recovery after spinal cord injury (SCI), yet clinical programming remains largely dependent on subjective parameter selection. This study evaluated high-density surface EMG (HD-sEMG)–derived spatial and temporal features as objective biomarkers for tSCS optimization in three adults with chronic cervical SCI. A 64-channel electrode array recorded stimulation-evoked responses across five cervical stimulation levels, four pulse widths, and graded amplitudes. Features describing activation magnitude, spatial distribution, cluster morphology, and temporal dynamics were extracted from epoch-based activation maps. Of the three enrolled participants, two demonstrated measurable stimulation-evoked responses and contributed to the paired-pulse analyses, whereas pulse-width analyses were limited to a single responsive muscle (left flexor carpi) in one participant. Paired-pulse analysis identified root mean square (RMS) as the most discriminative feature, revealing nonlinear, muscle- and level-specific dose–response relationships in which maximal suppression often occurred at intermediate rather than maximal amplitudes. Increasing pulse width expanded the spatial extent of recruitment (active area: p = 0.006; convex hull area: p = 0.004) without altering response timing. Polarity reversal analysis demonstrated stable innervation zone localization across stimulation levels and amplitudes. These findings establish a spatially resolved HD-sEMG framework that may support individualized tSCS parameter selection in SCI. Full article

Background: Neuromodulation is a rapidly developing field with growing interest in its application in neuro-oncology, particularly since the publication of the EF-14 trial which demonstrated a survival benefit conferred by tumour treating fields (TTF) in patients with glioblastoma. In addition, the emerging field of cancer neuroscience has postulated the role of neural–tumour communication in tumour aetiology, which is theoretically targetable by neuromodulation strategies. This scoping review therefore aims to comprehensively evaluate current or future applications of neuromodulation in managing patients with brain tumours, encompassing preclinical and clinical studies. Methods: The MEDLINE database was queried for all relevant articles from inception to 1 December 2024. A synthesis of findings was performed, broadly categorised to preclinical and clinical research. Findings: The database search returned 3296 results, from which 187 full-text articles were further assessed. A total of 79 studies met the inclusion and exclusion criteria and were included. The results from preclinical studies (n = 18) were stratified according to modality which included electrical therapy, electroporation, electromagnetic field (EMF) and deep brain stimulation (DBS). Similarly, clinical studies (n = 61) were classified to preoperative modalities such as transcranial magnetic stimulation (TMS) and transcranial direct stimulation (tDCS), and postoperative modalities such as TMS, TTF, EMF and spinal cord stimulation (SCS). Interpretation: The application of neuromodulation as adjunctive therapy in the context of neuro-oncology is an emerging field, with encouraging results in various modalities across a wide range of applications from surgical planning and functional rehabilitation, to its therapeutic potential. Further research is urgently needed to harness the potential of neuromodulation in improving patient outcomes. Full article

Background/Objectives: Pediatric spinal cord injury (SCI) is a rare yet highly disabling condition associated with substantial functional and psychosocial impairments. Although robot-assisted gait training (RAGT) and transcutaneous spinal cord stimulation (tSCS) have independently demonstrated promising results, evidence regarding their combined use in pediatric SCI is limited. This study aimed primarily to assess the feasibility and safety of combining RAGT with tSCS in children with incomplete SCI, and secondarily to explore its effects on clinical outcomes. Methods: A case series study was conducted that included three pediatric participants (<18 years) with chronic incomplete SCI (AIS C–D). Participants completed five consecutive sessions of RAGT using a Lokomat device combined with tSCS applied at the lumbosacral level. Each session consisted of 30 min of gait training, including 20 min of concurrent electrical stimulation. Safety was assessed through adverse-event monitoring and pain evaluation. Clinical outcomes included gait speed (10MWT), trunk control (SATCo), lower-limb strength (LEMS), and spasticity (MAS). Results: Session adherence reached 100%. Skin erythema was the most frequently reported adverse event and showed a clear association with tSCS. All participants demonstrated improvements in gait speed, with two exceeding the minimal clinically important difference. Secondary results showed similar outcomes for spasticity, strength, and trunk control, with no clinically meaningful changes in any case. Conclusions: The combined application of RAGT and tSCS appears to be a feasible and safe intervention for children with incomplete SCI. Preliminary findings suggest potential benefits in gait speed, thereby supporting the need for further investigation with larger samples and controlled study designs. Full article

Background: Spinal cord stimulation (SCS) is an established intervention for refractory chronic neuropathic pain, but response to trial stimulation and long-term benefit remain heterogeneous. Clinicians need practical tools to document patient-selection domains discussed in the neuromodulation literature without overstating the precision of currently available evidence. Methods: We conducted a narrative synthesis of randomized trials, cohort studies, registry analyses, systematic reviews, and consensus recommendations addressing SCS outcomes and candidate selection. The objective was not to derive or validate a multivariable prediction model, but to construct a transparent, bedside-oriented framework organizing clinically accessible domains relevant to SCS trial candidacy. Results: Six domains were incorporated into the proposed SCS Trial Success Score (STSS): primary indication, psychological status, smoking status, opioid burden, body mass index, and pain duration. The resulting 0 to 12 point score is presented as an evidence-informed clinical profile rather than a validated prognostic instrument. Three descriptive categories are proposed: more favorable profile, optimization-sensitive profile, and less favorable profile. These categories are intended to guide documentation, shared decision-making, and optimization of modifiable factors, not to determine eligibility automatically. Conclusions: Pending prospective validation, checklist-mode use is the preferred interim application of the STSS. The framework may support structured pre-trial assessment, identification of modifiable factors, and shared decision-making. It should not be used as a standalone numerical decision rule, to deny access to neuromodulation, or to replace multidisciplinary judgment. Prospective derivation, calibration, external validation, and decision-curve analysis are required before the STSS can be considered a clinical prediction rule. Full article

Spinal cord injury (SCI) is frequently accompanied by abnormal muscle tone and spasticity, which impair voluntary motor control, mobility, and quality of life. Although classically defined as velocity-dependent hyperreflexia, tone abnormalities after SCI encompass a broader spectrum, including sustained muscle activation, co-contraction, clonus, and non–velocity-dependent resistance to movement. These manifestations arise from distributed changes across spinal and supraspinal motor systems. At the segmental level, SCI induces maladaptive plasticity involving motoneurons, interneurons, sensory afferents, and muscle, including dysregulated persistent inward currents, altered inhibitory neurotransmission, afferent hyperexcitability, synaptic reorganization, and structural muscle remodeling. In parallel, supraspinal adaptations—including cortical motor map reorganization, reduced intracortical inhibition, corticospinal–reticulospinal imbalance, loss of monoaminergic modulation, and altered brainstem and cerebellar regulation—further amplify spinal circuit gain and impair inhibitory control of tone. Current pharmacologic treatments largely suppress symptoms without addressing these underlying circuit changes, while invasive neuromodulatory strategies are limited by surgical risk or state-dependent effects. This review synthesizes emerging insights into the multilevel mechanisms regulating abnormal tone after SCI and examines neuromodulatory approaches targeting spinal and supraspinal networks. Particular attention is given to transcutaneous spinal cord stimulation (TcSCS), a non-invasive method capable of modulating segmental reflex circuits and descending control pathways. Advances in transcriptomic and epigenetic profiling may further enable mechanism-based therapies and biomarker-guided strategies for treating spasticity. Full article

Background: Chronic pain is the leading cause of years lived with disability worldwide, with low back pain representing the most prevalent and disabling condition. Spinal cord stimulation (SCS) and intrathecal drug delivery (IDD) systems are established neuromodulation techniques for refractory chronic pain. However, a subset of patients experiences partial or declining benefit with either modality alone. In such cases, combined therapy may represent a rescue strategy. Methods: retrospective case series at a single center, including patients previously implanted with SCS who subsequently required IDD due to loss of efficacy or inadequate pain coverage. Pain intensity, opioid consumption, health-related quality of life, and patient satisfaction were assessed using validated instruments. Results: Twelve patients were included. Persistent low back pain with mixed nociceptive–neuropathic features was the most common indication. Combined therapy was observed in association with a mean reduction of 3.5 points on the Numeric Rating Scale, corresponding to an approximate 40% decrease in pain intensity. More than half of the patients discontinued systemic opioids. Complications occurred in seven patients (58.3%), mostly hardware-related and manageable with surgical revision; only one patient developed a device-related infection. Conclusions: In this case series, combined SCS and IDD therapy was observed in association with clinically meaningful pain reduction, decreased opioid use, and high patient-reported satisfaction. Although quality-of-life scores remained below population norms, patients consistently reported subjective improvement. Combined neuromodulation may represent a valid rescue option in selected patients with insufficient response to SCS alone. Full article

Spinal cord stimulation (SCS) is an established therapy for chronic pain, yet treatment response remains highly variable and patient selection largely empirical. The identification of biomarkers with the potential to predict and monitor therapeutic response is therefore critical for advancing toward precision neuromodulation. This study provides a structured narrative synthesis of current evidence on biomarkers in SCS, focusing on their predictive and monitoring roles and their translational potential. Available studies were analysed across electrophysiological, neuroimaging, autonomic, and molecular domains and conceptually organized into predictive biomarkers—reflecting baseline biological states associated with treatment susceptibility—and monitoring biomarkers, capturing physiological and molecular adaptations following stimulation. Among predictive approaches, intraoperative electroencephalography (EEG) and resting-state functional magnetic resonance imaging (rs-fMRI) have shown promising but exploratory discriminative performance. However, EEG findings are derived from intraoperative settings, limiting their applicability to pre-implantation patient selection. In contrast, monitoring biomarkers—including heart rate variability, metabolic imaging, and immunological parameters—provide objective measures of treatment-induced changes but do not currently support predictive use. Molecular and genomic biomarkers, while mechanistically informative, remain exploratory and lack validated clinical utility. A central limitation of the field is the fragmentation of biomarker research, with most studies evaluating single modalities in isolation. To address this gap, we propose a translational framework integrating predictive and monitoring biomarkers through a two-stage model combining baseline stratification with longitudinal response assessment. Although biomarker research in SCS is rapidly evolving, its clinical application remains limited. The development of multimodal, validated biomarker strategies may support improved patient selection and more objective evaluation of treatment response, enabling a transition toward mechanism-based neuromodulation. Full article

“Spinal cord stimulation (SCS)” is an established therapy for chronic pain and an emerging modality for functional recovery after spinal cord injury (SCI) and other clinical applications. Despite its clinical potential, current implantable SCS systems remain constrained by high power consumption, limited adaptability, device size, and long-term stability. Recent advances in closed-loop neuromodulation and integrated circuit (IC) design are enabling more adaptive, efficient, and miniaturized SCS systems. This narrative review focuses on integrated circuit and system-on-chip (SoC) architectures that enable more advanced closed-loop SCS modalities, including stimulation, sensing, and wireless power/data subsystems. Specifically, the present work examines stimulation drivers and charge-balancing circuits that ensure safe and precise current delivery, wireless power transfer, telemetry methods which maintain reliable energy and data flow in implanted systems, and analog front-end circuits that enable closed-loop biopotential monitoring for adaptive feedback control. It aims to highlight innovations in IC design, energy harvesting, and wireless communication strategies while discussing trade-offs in power efficiency, die area, thermal limits, and biocompatibility. Emerging trends emphasize miniaturized and adaptive neural implants that integrate circuit-level efficiency with therapeutic flexibility, thereby advancing the next generation of closed-loop neuromodulation technologies. Ultimately, innovations in microelectronics are paving the way for enhanced long-term efficacy, safety, and clinical applicability of implantable SCS systems to optimize functional impacts. Full article

Background: Transcutaneous spinal cord stimulation (tSCS) is a promising approach to enhance functional recovery after spinal cord injury (SCI). However, evidence on repeated sessions and their effects on gait and lower-limb strength remains limited. This study evaluated the effects of multisegmental tSCS on walking ability, muscle strength, and functional independence in individuals with SCI. Methods: In this randomized controlled trial with a partial crossover design, twelve individuals received tSCS combined with gait rehabilitation, while ten underwent gait rehabilitation alone, for three weeks. Four participants crossed over to the tSCS group after a minimum one-week washout period following the control intervention. We assessed the American Spinal Injury Association Impairment Scale (AIS), Total Motor Score (TMS), Lower Extremity Motor Score (LEMS), Walking Index for Spinal Cord Injury II (WISCI-II), 10- and 6-Meter Walking Tests (10MWT, 6meterWT), Timed Up and Go (TUG) test, maximal voluntary contraction (MVC) of the quadriceps (QM) and tibialis anterior (TA), and the Spinal Cord Independence Measure (SCIM-III); tSCS was applied at three spinal segments during gait rehabilitation over 15 sessions. Results: tSCS significantly improved MVC in both muscles, as well as SCIM-III and TUG, and these improvements were maintained at follow-up, with no significant adverse events reported. Other clinical assessments also showed significant improvement in both groups. Conclusions: tSCS was well tolerated and conferred additional benefits in lower-limb muscle strength, walking ability (as assessed by TUG), and functional independence, supporting its potential as a valuable adjunct to rehabilitation. Full article

Background/Objectives: Spinal cord stimulation (SCS) is an established therapy for chronic refractory pain, but its clinical value depends on whether benefit persists beyond the early post-implant period. Although short-term SCS studies are abundant, reports with follow-up of 24 months or longer are dispersed, methodologically heterogeneous, and difficult to interpret across indications and stimulation platforms. This scoping review aimed to map the clinical literature reporting SCS outcomes at ≥24 months, characterize the represented populations and modalities, summarize the long-term outcome domains assessed, and identify major methodological and clinical gaps in the evidence base. Methods: This PRISMA-ScR-informed scoping review applied a Population–Concept–Context framework. PubMed/MEDLINE and Scopus were searched through April 2026, yielding 6866 records before deduplication. Following staged title/abstract screening, iterative full-text retrieval, and the reconciliation of overlapping publications, 292 unique full-text reports were assessed for eligibility. Studies reporting original clinical SCS data with extractable outcomes at ≥24 months were included. No meta-analysis or formal GRADE assessment was undertaken, as the objective was evidence mapping rather than pooled effect estimation. Results: The final evidence map comprised 65 unique reports representing a cumulative report-level population of 11,518 participants across non-overlapping cohorts. The literature was dominated by non-randomized evidence (55 observational reports; 10 randomized or randomized-derived). The most frequent indication was mixed chronic pain (30/65; 46.2%), followed by failed back surgery syndrome/persistent spinal pain syndrome (FBSS/PSPS; 16/65; 24.6%), chronic back and/or leg pain (6/65; 9.2%), complex regional pain syndrome (CRPS; 5/65; 7.7%), and painful diabetic neuropathy (PDN; 4/65; 6.2%). Most reports involved conventional or unspecified SCS (47/65; 72.3%), with smaller contemporary clusters for 10 kHz high-frequency SCS and ECAP-controlled closed-loop SCS. The most frequently reported outcome domains were pain durability, function and quality of life, device-related outcomes, and opioid use. At a descriptive level, the literature more often supported persistence of benefit than complete erosion of effect, particularly in spinal pain populations and in contemporary PDN and closed-loop SCS cohorts. Interpretation was constrained by outcome heterogeneity, cohort overlap, mixed indication categories, and inconsistent opioid and device-maintenance reporting. Conclusions: The long-term SCS literature supports the view that durable benefit is achievable in a substantial patient subset, particularly in FBSS/PSPS populations, and in more recent evidence, in PDN, nonsurgical refractory back pain, and closed-loop SCS cohorts. The evidence base remains heterogeneous and does not support a uniform certainty-ranked estimate across indications and technologies. Future studies should prioritize indication-specific cohorts, standardized multidomain outcome reporting, and transparent separation of unique cohorts from secondary analyses of the same clinical populations. Full article