Search Results (147)

Spinal cord injury (SCI) research has long treated the glial scar as the central obstacle to regeneration. That view is useful, but it is now too narrow. The scar is not a passive wall. It is an evolving repair tissue that contains inflammation, stabilizes the lesion, remodels extracellular matrix, and, under many conditions, restricts axonal growth. The next phase of SCI therapy should therefore move from scar suppression to scar reprogramming. In this Opinion, I argue that the field should prioritize temporally precise, spatially targeted, and biomarker-guided interventions that preserve the protective functions of the scar while reducing its chronic inhibitory features. Cell transplantation, biomaterials, neurotrophic factors, gene therapy, immunomodulation, and neuromodulation each offer important strengths, but none is sufficient as a stand-alone regenerative therapy. The most credible path forward is a staged combinatorial strategy that converts the lesion microenvironment into a permissive, instructive, and trainable tissue bridge. 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: Spasticity is one of the most disabling manifestations of multiple sclerosis (MS), contributing to limitations in walking and transfers, pain, progressive functional limitation, and reduced quality of life. Despite advances in rehabilitation, pharmacological therapies, botulinum toxin injections, and intrathecal baclofen, many patients continue to experience refractory focal or multifocal spasticity requiring alternative therapeutic approaches. Percutaneous cryoneurolysis has recently emerged as a minimally invasive peripheral neuromodulation technique capable of selectively reducing pathological muscle overactivity through reversible axonotmesis while preserving the structural framework necessary for nerve regeneration. Growing clinical experience has expanded its application across several neurological disorders; however, its role in MS has not yet been comprehensively defined. Methods: A structured narrative review was conducted through comprehensive searches of PubMed/MEDLINE, Scopus, and Web of Science. Original clinical studies evaluating percutaneous cryoneurolysis for neurological spasticity were identified and critically synthesized. Because disease-specific evidence in MS remains limited, studies involving other upper motor neuron disorders, including stroke, cerebral palsy, traumatic brain injury, and spinal cord injury, were also considered to provide a broader overview of current clinical applications, procedural techniques, safety, and functional outcomes. Results: The available evidence includes case reports, case series, and prospective and retrospective observational studies, together with recent evidence syntheses. Across different neurological conditions, ultrasound-guided cryoneurolysis has consistently demonstrated technical feasibility and a favorable safety profile, with reported reductions in spasticity, improvements in passive range of motion, pain reduction, facilitation of positioning and nursing care, and, in selected studies, improved functional performance. Recent observational cohorts and prospective studies have expanded the evidence base by providing larger patient populations and longer follow-up, while systematic evidence syntheses have confirmed the growing clinical interest in this technique. Nevertheless, substantial heterogeneity persists regarding patient selection, target nerves, procedural protocols, outcome measures, and duration of follow-up. Evidence specifically addressing patients with MS remains limited and is currently derived primarily from individual case reports and small clinical series. Conclusions: Current evidence suggests that percutaneous cryoneurolysis represents a promising minimally invasive adjunctive treatment for selected patients with focal or multifocal neurological spasticity, including those with multiple sclerosis. However, the available evidence remains predominantly observational, and randomized controlled trials comparing cryoneurolysis with established therapies are still lacking. Future multicenter prospective studies, standardized treatment protocols, and disease-specific investigations are required to better define patient selection, long-term efficacy, safety, and the role of cryoneurolysis within contemporary multidisciplinary spasticity management. 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

Closed-loop neuromodulation systems for spinal cord injury (SCI) comprise a sensor layer that detects motor state or intent, a controller that converts this information into stimulation commands, and a stimulation interface that modulates spinal, peripheral, or supraspinal circuits. Although neuromodulation has shown potential for improving stepping, standing, trunk control, and upper-limb function after SCI, the performance of closed-loop systems depends critically on their reliability, latency, and practicality. This structured narrative review focuses on the sensor inputs used in closed-loop neuromodulation for SCI, including kinematic sensors, electromyography, force and pressure sensors, vision-based sensing, and emerging neural interfaces. We summarize how these signals have been used to estimate gait phase, posture, motor intent, and task state, and how sensor-driven strategies have progressed from animal models to early clinical applications. Preclinical studies provide mechanistic insights into activity-dependent, phase-specific, and proprioceptive feedback-mediated control, whereas human studies suggest that sensor-guided stimulation may improve functional specificity; however, comparative evidence remains limited. Future translation will require robust multimodal sensing, standardized reporting of latency and calibration burden, and practical designs suitable for supervised clinical and, ultimately, home use. 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: Same-day or post-admission cancellation of elective surgery is associated with inefficient operating room utilization, patient distress, and disruption of coordinated perioperative care. Functional neurosurgery is particularly vulnerable to late-stage cancellation because procedural readiness depends on parallel clinical, anatomical, medication-related, device-related, and systemic considerations. Objective: This paper aims to describe the implementation of a structured preoperative review framework for functional neurosurgery and to evaluate its association with late-stage surgical cancellation after patient admission. Methods: We performed a retrospective single-center before-and-after study of consecutive functional neurosurgical procedures scheduled at Sheba Medical Center between January 2020 and December 2025. The ABCDE framework was introduced in 2023 as a structured workflow model organized around five domains: Anatomy, Bacteria, Clotting, Devices, and Elsewhere. Included procedures were deep brain stimulation, vagus nerve stimulation, focused ultrasound, intrathecal pump implantation or replacement, implantable pulse generator replacement, spinal cord stimulation, peripheral nerve stimulation, and other palliative neuromodulation procedures. The primary endpoint was late-stage cancellation, defined as cancellation after hospital admission and initiation of operative preparation. The primary comparison was between 2020–2022 and 2023–2025. A sensitivity analysis excluded 2020 because of pandemic-era disruption. Results: A total of 867 procedures were scheduled. Late-stage cancellation occurred in 16 of 407 pre-implementation procedures and 5 of 460 post-implementation procedures, corresponding to rates of 3.9% and 1.1%, respectively. The absolute risk difference was −2.8 percentage points (95% CI, −5.2 to −0.8), and the relative risk for cancellation after implementation was 0.28 (95% CI, 0.10 to 0.75). A two-sided Fisher’s exact test comparing cancellation versus non-cancellation across the pre-implementation and post-implementation periods was statistically significant (16/407 vs. 5/460; p = 0.0074). After excluding 2020, the direction of effect remained similar, but the difference was not statistically significant: 8 of 302 procedures in 2021–2022 were canceled compared with 5 of 460 in 2023–2025 (2.6% vs. 1.1%; p = 0.15). Detailed source-level attribution was incomplete for 10 of 21 cancellation events, and domain-level analyses should therefore be interpreted descriptively. Conclusions: Implementation of the ABCDE framework was associated with fewer late-stage surgical cancellations in this single-center before-and-after study. Because the design is observational, the number of events is small, and the study period overlaps with pandemic-era disruption and post-pandemic service stabilization, the findings should be interpreted as hypothesis-generating rather than causal. The framework may provide a practical structure for standardizing preoperative review in functional neurosurgery, but prospective studies with formal adherence tracking and procedure-specific analyses are needed. 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

Background: Pelvic floor dysfunction (PFD) is frequent in neurological disorders, but it is often approached as a secondary urological or gynecological problem rather than a functional rehabilitation target. Neurological disease can disturb cortical, pontine, spinal, sacral, autonomic, somatic, and sensory pathways that regulate bladder storage, voiding, bowel evacuation, sexual function, and pelvic pain modulation. Methods: This narrative review synthesized biomedical evidence identified through PubMed searches from database inception to 2 May 2026. Search concepts included neurogenic lower urinary tract dysfunction, urinary and bowel dysfunction, sexual dysfunction, pelvic pain, pelvic floor rehabilitation, biofeedback, electrical stimulation, neuromodulation, telerehabilitation, robotics, and major neurological disorders. The review was oriented according to the Scale for the Assessment of Narrative Review Articles (SANRA) and was not designed as a systematic review or meta-analysis. Results: Evidence from multiple sclerosis, stroke, Parkinson’s disease, Alzheimer’s disease and related dementias, spinal cord injury, and fibromyalgia or nociplastic pain syndromes supports a phenotype-based framework in which pelvic floor muscle training, bladder and bowel training, biofeedback, neuromuscular electrical stimulation, posterior tibial nerve stimulation, sacral neuromodulation, telerehabilitation, robotics, and multidisciplinary care are considered complementary rather than interchangeable strategies. Conclusions: PFD in neurological disorders may be more appropriately conceptualized as a multidimensional neurorehabilitation target. Effective care depends on disease-informed phenotyping, individualized rehabilitation goals, attention to cognition and adherence, and standardized outcome measurement. Future studies should test phenotype-specific pathways that integrate bladder, bowel, sexual, pain, participation, safety, and caregiver outcomes. 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: 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