Search Results (165)

Background/Objectives: Neuromuscular electrical stimulation (NMES) is a promising adjunct to activity-based training for individuals with spinal cord injury (SCI). While lower extremity NMES applications are well documented, upper extremity (UE) outcomes remain underexplored in pediatric SCI. The objective of this case series was to evaluate outcomes following a combined NMES and activity-based therapy program targeting the UE in children with chronic SCI. Methods: In this retrospective case series, we analyzed outcomes from five children, ages 4 to 15 years old, with chronic cervical level SCI who completed an individualized activity-based training program with concurrent wide pulse neuromuscular electrical stimulation (WPS-NMES). Participants were children with chronic SCI (≥6 months post-injury). Functional assessments were conducted by pre- and post-intervention. Pre- and post-intervention outcomes were summarized descriptively at the individual case level. Results: Five children with chronic cervical SCI (ages 4–15 years) completed a mean of 54 intervention sessions. All patients demonstrated improved trunk control, with Segmental Assessment of Trunk Control (SATCo) increases of 1–6 points. UE gains on the Peds-NRS were observed in 4/5 patients, primarily in overhead reach and object-to-mouth items. Box and Blocks Test scores improved in 4/5 patients in at least one UE, while one patient remained at 0 bilaterally, and one patient experienced a unilateral decline. One patient demonstrated proximal and trunk improvements without changes in manual dexterity. No unanticipated adverse events were reported. Conclusions: Observed improvements in selected trunk and UE outcomes occurred during participation in a multimodal rehabilitation program incorporating WPS-NMES. These preliminary findings describe functional changes observed during the rehabilitation program and may help inform the design of future controlled studies evaluating multimodal rehabilitation approaches for children with chronic SCI. Full article

Background: Spinal cord injury (SCI) is associated with persistent motor impairment, neuropathic pain, and reduced quality of life. While spinal cord stimulation (SCS) is an established therapy for neuropathic pain, motor effects have largely been demonstrated in experimental settings with activity-based training protocols. Whether such effects can be achieved within routine clinical care remains unclear. Case Presentation: We report on motor effects after the clinical implementation of percutaneous SCS using a commercially available system in a patient with chronic, posttraumatic, incomplete thoracic SCI. Following a standard inpatient trial and implantation of two percutaneous leads for neuropathic pain, all subsequent management, programming, and rehabilitation were conducted in an outpatient setting. Task-specific stimulation programs were iteratively developed to support functional activities during routine rehabilitation. Lower-extremity muscle strength was assessed using standardized handheld dynamometry at baseline and at monthly intervals over six months under stimulation-ON and stimulation-OFF conditions. Results: Serial dynamometry showed early stimulation-associated increases in force generation, with higher values under stimulation-ON than stimulation-OFF conditions. Over time, absolute strength values under OFF conditions also increased across individual muscle measurements, while stimulation-associated ON–OFF differences became less pronounced during intermediate follow-up but remained evident at month six. These observations included both acute stimulation-associated differences in force generation and longitudinal improvements in OFF-state motor performance. Stimulation was well tolerated during daily use and successfully integrated into outpatient rehabilitation. Functional outcomes showed concordant improvements in ambulatory performance and patient-reported domains. No stimulation-related adverse effects were observed during follow-up. Conclusions: This case illustrates how clinically indicated percutaneous SCS can be combined with motor-oriented programming within routine outpatient rehabilitation. The observed stimulation-associated motor effects and longitudinal changes in stimulation-OFF strength are limited to this individual patient and cannot establish efficacy or causality. Prospective controlled studies are needed to determine the reproducibility and clinical relevance of these observations in chronic incomplete SCI. Full article

Background/Objectives: Epidural electrical stimulation (EES) is a valuable intervention for motor recovery after spinal cord injury (SCI). However, evaluating expected outcomes can be challenging due to the difficulty of assessing residual functional connectivity and other key factors underlying the effects of EES. This case study investigates EES with two 8-contact percutaneous electrodes (Perc-EESs) as a prognostic tool and therapeutic bridge for chronic neuromodulation with EES in an individual with clinically motor-complete SCI. Methods: A 40-year-old male (AIS-B, Th5–Th6, >20 years since initial presentation followed by a complex history of progressive deterioration and two subsequent neurosurgical interventions) underwent a 7-day trial using Perc-EES, followed by chronic 5-6-5 Medtronic lead (Paddle-EES) implantation at the L2–S1 segments. Volitional motor control and EMG activity was assessed across three stages: Perc-EES at 5, 7, and 10 days post-enrollment; Paddle-EES at 13, 15, and 18 days post-enrollment; and at a 1-year follow-up (Paddle-EES (1y)). Evaluations were performed in side-lying and upright positions. Results: Without EES, no visible movements were observed. Perc-EES facilitated rhythmic EMG activity and initial voluntary movements, providing an early proof-of-concept that Perc-EES could serve as a preliminary assessment of the patient’s responsiveness to neuromodulation. Paddle-EES (1y) demonstrated a further improvement in motor coordination. Analysis using the Rudolph coefficient showed a distinct shift toward zero. This shift reflects stimulation-associated changes in EMG coordination, moving away from co-activation toward a more alternating activation pattern across side-lying and upright positions. Conclusions: This single-patient feasibility case study suggests that trial Perc-EES may have potential in determining the long-term benefits of chronic Paddle-EES in motor activation after SCI. While these conclusions remain preliminary, these findings can further serve as a potential diagnostic tool to optimize electrode placement and enhance overall recovery in motor-complete SCI patients. Full article

Background: Urinary tract infections (UTIs) are a leading cause of morbidity in patients with chronic spinal cord injury (SCI). This study examined the incidence of first and recurrent symptomatic UTIs in patients with chronic SCI and explored clinical factors associated with infection risk, with particular attention to bladder management methods and structural urinary tract abnormalities. Methods: We conducted a longitudinal observational study including 297 patients with chronic SCI (≥5 years post-injury; 215 males, 82 females with a mean age of 49.1 ± 13.8 years). Participants underwent regular evaluations, including kidney ultrasounds, videourodynamic studies (VUDS), and effective renal plasma flow (ERPF) measurements. Symptomatic UTIs were strictly defined using clinical–microbiological criteria to exclude asymptomatic bacteriuria (ASB). Clinical outcomes were evaluated over a minimum 5-year follow-up period. Results: Average annual symptomatic UTI rates were 0.31 ± 0.37 (major), 0.46 ± 0.47 (minor), and 0.77 ± 0.64 (total) episodes per patient-year. Bladder management method significantly influenced UTI rates (p < 0.001), with the highest rates observed in patients with indwelling urethral catheters (IUC) (1.19 ± 0.71), followed by suprapubic cystostomy (SPC) (0.91 ± 0.54), clean intermittent catheterization (CIC; 0.59 ± 0.47), and reflex voiding (0.31 ± 0.36). Recurrence (≥2 episodes) occurred in 23.9% of patients with indwelling catheters, 26.9% with suprapubic cystostomy, 13.0% with CIC, and 7.5% with reflex voiding. Patients with indwelling urethral catheters had higher total UTI rates and a higher recurrence rate than those with suprapubic cystostomy (1.19 vs. 0.91 episodes per patient-year; recurrence 38.8% vs. 26.9%). Hydronephrosis (Adjusted OR = 4.78, 95% CI: 2.45–9.32, and p < 0.001), bladder wall trabeculation (Adjusted OR = 3.65, 95% CI: 1.92–6.94, and p < 0.001), and indwelling catheter use (IUC + SPC) (Adjusted OR = 3.41, 95% CI: 1.85–6.29, and p < 0.001) were independently associated with increased UTI risk. Conclusions: Indwelling catheter use and specific structural upper and lower urinary tract abnormalities were independently associated with an increased risk of symptomatic UTIs in chronic SCI. Prioritizing CIC, routine monitoring with imaging and urodynamics, and implementing targeted preventive strategies may help reduce infection burden and preserve renal function. Full article

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: Subjective experience is increasingly recognised as an important component of brain–computer interface (BCI) performance in extended reality (XR) environments. Although embodiment and simulator sickness are known to influence user experience, their relationships with cortical activity during XR–BCI operation remain poorly understood. Building upon our previous investigations of embodiment and simulator sickness in XR–BCIs, the present study examined whether these subjective dimensions are associated with distinct neurophysiological patterns during repeated XR–BCI use in a participant with chronic spinal cord injury (SCI). Methods: Seventeen XR–BCI sessions performed by a participant with chronic complete SCI were analysed. Bayesian correlation analyses examined associations among embodiment, simulator sickness, BCI performance, and EEG activity. Multiple linear regression was used to identify variables independently associated with sensorimotor beta activity, and the robustness of the regression findings was evaluated using bootstrap estimation and leave-one-out sensitivity analyses. Results: Bayesian analyses identified two principal patterns of association. Sense of embodiment was positively associated with frontal theta activity (F3), whereas simulator sickness showed a negative association with sensorimotor beta activity (C3–C4). As expected, classifier acquisition accuracy was strongly associated with subsequent BCI performance. Multiple regression demonstrated that simulator sickness was the only variable independently associated with C3–C4 beta activity after accounting for embodiment and BCI performance. This association remained robust following bootstrap estimation and leave-one-out sensitivity analyses. Conclusions: Although limited to a single participant, these findings suggest that different dimensions of subjective experience during XR–BCI operation are associated with partially distinct neurophysiological correlates. In particular, simulator sickness was the variable most consistently associated with sensorimotor beta activity across all analyses. These findings provide a foundation for future longitudinal investigations of the neural mechanisms linking subjective experience and cortical dynamics during XR–BCI use. Full article

Background: Individuals with spinal cord injury (SCI) frequently experience chronic pain, trunk instability, and respiratory dysfunction. This pilot trial investigated the synergistic effects of a combined neuro-orthotic approach (thoracolumbosacral orthosis (TLSO) plus transcutaneous electrical nerve stimulation (TENS)) versus TLSO alone on pain, trunk control, and respiratory function in chronic incomplete SCI. Methods: Twelve adults with chronic incomplete SCI (T6–T12) were randomized to a combined group (TLSO + TENS) or a control group (TLSO alone) for a four-week intervention. Outcomes included pain (Visual Analogue Scale), trunk control (Trunk Assessment Scale), and respiratory function (tidal volume [VT], respiratory rate [RR], oxygen uptake [VO₂], ventilatory equivalent for oxygen [VE/VO₂], and inspiratory duty cycle [Ti/Ttot]) assessed at three time points (before intervention, immediately after intervention, and after one month). Results: The combined group demonstrated a significant reduction in pain (47.8% vs. 10.4%, p = 0.01) and an improvement in Ti/Ttot (33.3% vs. 4.9%, p = 0.008) compared to the control group. Both groups showed significant improvements in VT and RR over time (p < 0.05), reflecting the biomechanical benefits of TLSO. Conclusions: Integrating TENS with TLSO offers a non-invasive strategy for managing chronic pain and improving respiratory pattern coordination in incomplete SCI. While TLSO optimizes basic ventilatory mechanics, adding TENS significantly enhances neural drive for efficient breathing and pain gating. Future large-scale trials incorporating active task-specific training are needed to restore functional trunk control. 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

Spinal cord injury (SCI) often results in varying degrees of motor and sensory dysfunction with limited potential for recovery. Research into in vivo astrocyte-to-neuron reprogramming has led to promising results that, if translated to SCI, could offer substantial therapeutic benefit by replenishing lost populations of neurons for functional restoration. Previous studies have shown that AAV9-mediated delivery of NeuroD1 is capable of reprogramming astrocytes into neurons in vivo after chronic SCI in rats. Here we evaluate the dose-dependent functional and neuroprotective potential of the NeuroD1 gene therapy platform for acute and subacute SCI in rats. The Cre-dependent, DIO-based AAV9-NeuroD1 gene therapy platform was administered directly into the spinal cord of female Long-Evans rats after moderate, thoracic level 8/9 contusion SCI at one of two intervention timepoints: immediately after injury (acute) or 1 week post-contusion (subacute). The viruses were administered at a titer of 10¹¹ or 10¹³ GC/mL. We demonstrate that the AAV9-NeuroD1 reprogramming platform successfully, albeit variably, transduced spinal cells that persisted up to 6 weeks post-injury. However, histological analysis revealed substantial neuronal off-targeting, suggesting a lack of astrocyte-specific targeting from the AAV9 DIO-based delivery platform. Surprisingly, we also found titer- and intervention timing-dependent effects on motor function and tissue preservation—as demonstrated by 1–2 point decrease in BBB scoring and near 50% increase in peak lesion cavitation area—when AAV9-NeuroD1 was administered immediately after SCI. While did not find any effects of the AAV9-NeuroD1 platform on sensory function or neuroinflammatory cell density, a subset of NeuroD1 signal reflected phagocytic uptake by Iba1 and CD68-expressing microglia/macrophages. These results indicate that the NeuroD1 reprogramming platform can exacerbate injury-related functional deficits when administered in the acute stage of injury, but has neuroprotective benefit on tissue preservation when administered in the subacute stage of injury. Our study demonstrates that several factors must be considered, including viral titer and intervention timing, to assess the therapeutic potential of AAV9-NeuroD1-mediated reprogramming for SCI. Full article

This pilot study examined longitudinal changes in psychological distress and biomarkers related to stress, inflammation, and biological aging during the first inpatient rehabilitation after Spinal Cord Injury (SCI). We analyzed data from 120 participants in the SwiSCI inception cohort at two timepoints: the beginning of the first post-injury rehabilitation and discharge. A subset of 50 participants representing four distress patterns (high chronic, low, transient, increasing distress) underwent biomarker analyses, including measurements of immune and inflammatory proteins and whole-blood transcriptomic profiling. The results showed that psychological distress, depression, and protein carbonyl content decreased significantly by discharge. In contrast, cortisol levels and telomere length showed no significant changes. Proteomic analyses revealed a broad downregulation of inflammatory proteins (e.g., IFN-γ, IL-10, LIF) at discharge, whereas transcriptomic profiles did not differ between timepoints. The high chronic distress group showed lower expression of six genes involved in adaptive immunity, neural development and apoptosis. Psychological distress was not linearly associated with global biomarker profiles. However, CXCL1 and IL-7 showed low-to-moderate correlations with depression and anxiety, respectively. This pilot study demonstrates the feasibility of integrating psychological and molecular data to investigate biological response following SCI. The findings are exploratory and need validation in larger studies with longer follow-up periods. Full article

Background/Objectives: Spinal cord injury (SCI) frequently leads to impaired respiratory function and increased pneumonia risk due to reduced respiratory muscle strength, altered thoracic compliance, autonomic dysregulation, and diaphragm displacement. This guideline aims to ensure appropriate, high-quality, and quality-assured care for individuals requiring respiratory support. Methods: This work represents a consensus-based S2k guideline developed by the “BeAtmung” working group of the German-speaking Medical Society for Paraplegiology (DMGP), in collaboration with experts from Germany and Switzerland, and endorsed by eight professional societies. Development followed the German Association of the Scientific Medical Societies (AWMF) guidance manual. Topics were defined in editorial meetings, supported by targeted literature searches and existing guidelines. Drafts were revised regularly with written feedback and final approval was granted after a consensus conference on 18 January 2022. Results: The guideline includes 11 specific recommendations addressing ventilation, monitoring, care structures, and discharge planning. Recommendations were graded using a three-level scheme (“need,” “should,” and “can be considered”) and consensus strength was classified as strong (>95%), consensus (>75–95%), majority (>50–75%), or no consensus (<50%). These recommendations support clinical decision-making and promote standardised, high-quality respiratory care for people with SCI. Conclusions: This guideline provides consensus-based recommendations for the comprehensive respiratory management of individuals with acute and chronic SCI, integrating diagnostic, therapeutic, and long-term care strategies to support high-quality, coordinated care across settings and healthcare systems. Full article

Neuropathic pain (NP) arises from diverse conditions, including peripheral nerve injury, spinal cord injury (SCI), and painful diabetic neuropathy, yet these disorders share oxidative stress, mitochondrial dysfunction, lipid dysregulation, and altered neuronal excitability. We investigated whether dietary omega-3 polyunsaturated fatty acids modulate ferroptotic stress-associated pathways, defined as lipid peroxidation susceptibility and impaired antioxidant defense rather than overt ferroptotic cell death. Female Sprague–Dawley rats received either a soy oil control diet (SOD) or fish oil omega-3-enriched diet (FOD) before chronic constriction injury (CCI). Behavioral outcomes were assessed using Hargreaves and CatWalk testing, followed by dorsal root ganglion (DRG) RNA sequencing, RT-PCR, and GPX4 ELISA. Previously generated SCI metabolomics and human diabetic serum metabolomic/lipidomic datasets were re-analyzed for shared pathways. FOD attenuated CCI-induced thermal hypersensitivity and improved gait parameters. DRG transcriptomics showed reduced injury-associated transcriptional disruption, enrichment of selenoamino acid metabolism, nonsense-mediated decay, and ribosomal quality-control pathways, and reduced mitochondrial dysfunction pathway activity. Omega-3 increased Gpx1/Gpx4 expression and GPX4 protein, reduced pain-associated genes including Scn10a, Piezo2, Trpa1, and Oprm1, and aligned with selenoamino acid enrichment in SCI and human datasets. Human lipidomics showed MG/DG/PC/PE pathway remodeling. These findings support ferroptotic stress as a plausible shared downstream mechanism modulated by omega-3 supplementation across NP models. 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/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

Spinal cord injury (SCI) is a major cause of long-term disability and is frequently accompanied by chronic pain, substantially reducing quality of life. Although spinal neuroinflammation is a recognized contributor to neuropathic pain, the role of supraspinal neuroinflammation remains less well defined. This systematic review critically evaluated experimental evidence linking SCI-induced supraspinal neuroinflammation with pain-related behaviors in animal models. A systematic literature search in PubMed, Web of Science Core Collection, and Scopus identified studies published over the last 20 years using rodent SCI models that assessed both supraspinal neuroinflammatory markers and pain-related behaviors. After screening, nine studies met the predefined criteria. The analyzed studies suggested that SCI is associated with supraspinal neuroinflammatory alterations, including increased microglial and astrocytic activation and upregulation of pro-inflammatory cytokines and chemokine-related pathways, in several brain regions. In intervention studies, reduced neuroinflammation was accompanied by improvement in mechanical or thermal pain-related behaviors. However, considerable methodological heterogeneity and moderate to high risk of bias were observed. Current evidence suggests an association between supraspinal neuroinflammatory alterations and chronic pain-related behaviors after SCI, but the limited number of studies and methodological variability restrict firm conclusions. Further well-designed experimental studies are needed to clarify underlying mechanisms. Full article