Search Results (245)

Spinal cord injury (SCI) is a debilitating condition that results from a culmination of acute and chronic damage to neural tissue, specifically the myelin sheath, thus impacting neurons’ abilities to synergistically perform their physiological roles. This review explores the molecular underpinnings of myelination, demyelination, and remyelination, emphasizing the role of oligodendrocyte progenitor cells (OPCs), astrocytes, and microglia in physiological, and pathophysiological, healing. Furthermore, we link these processes with emerging therapeutic strategies currently under investigation in animal and human models, underscoring areas of translational medicine that remain underutilized. The goal of this review is to provide a framework for developing more advanced interventions to restore function and improve outcomes for individuals with SCI. Full article

Background/Objectives: This study investigated variations in DNA methylation patterns associated with chronic pain and propensity for recurrent pressure injuries (PrI) in persons with spinal cord injury (SCI). Methods: Whole blood was collected from 81 individuals with SCI. DNA methylation was quantified using Illumina genome-wide arrays (EPIC and EPICv2). Comprehensive clinical profiles collected included secondary health complications, in particular current PrI and chronic pain. Relationships between recurrent PrI and chronic pain and whether the co-occurrence of both traits was mediated by changes in DNA methylation were investigated using R packages limma, DMRcate and mCSEA. Results: Three differentially methylated positions (DMPs) (cg09867095, cg26559694, cg24890286) and one region in the micro-imprinted locus for BLCAP/NNAT are associated with chronic pain in persons with SCI. The study cohort was stratified by PrI status to identify any sites associated with chronic pain and while the same three sites and region were replicated in the group with no recurrent PrI, two novel, hypermethylated (cg21756558, cg26217441) sites and one region in the protein-coding gene FDFT1 were identified in the group with recurrent PrI. Gene enrichment and genes associated with specific promoters using MetaScape identified several shared disorders and ontology terms between independent phenotypes of pain and recurrent PrI and interactive sub-groups. Conclusions: DMR analysis using mCSEA identified several shared genes, promoter-associated regions and CGI associated with overall pain and PrI history, as well as sub-groups based on recurrent PrI history. These findings suggest that a much larger gene regulatory network is associated with each phenotype. These findings require further validation. Full article

Background/Objectives: Spinal cord injuries (SCIs) are among the most debilitating conditions and are a leading cause of disability in young people. This study aimed to analyze the causes of SCIs, assess injury severity using the AIS scale, and evaluate complications during rehabilitation in a hospital setting. Methods: The study involved 176 individuals with SCI, including 142 with a traumatic SCI (TSCI) and 34 with a non-traumatic SCI (NTSCI), rehabilitated at various times post-injury. The data on injury causes, paresis type, complications, wheelchair use, gender, age, and treatment methods were collected. The injury severity was assessed using the AIS. Results: A significant gender difference was found between the TSCI and NTSCI groups (85.2% male vs. 61.8% male). TSCI individuals were also younger. The causes of TSCI were traffic accidents, falls from height, and diving, while the causes for NTSCI included spinal ischemia, tumors, degenerative disc disease, and inflammation. TSCI individuals had more AIS A lesions (52.8% vs. 26.5%) and more cervical injuries (53.5% vs. 14.7%), whereas NTSCI individuals had more AIS C lesions (38.2% vs. 18.3%) and thoracic damage (58.8% vs. 35.2%). TSCI patients were more often treated surgically (95.7% vs. 61.8%) and used wheelchairs (88% vs. 55.9%). No significant differences were found in terms of complications between the groups, though TSCI individuals underwent more chronic rehabilitation. Conclusions: Our research shows that there are significant differences between TSCI and NTSCI both in terms of the level of damage and the severity of damage to neural structures (AIS scales), and thus significant differences in the patients’ functioning in later life for both groups of individuals. Full article

Background: Spinal cord injury is a multisystem disease which compromises independence and quality of life; remote care models represent an opportunity for long-term management of complications. The aim of this study was to explore remote care models for chronic spinal cord injury patients. Methods: A systematic review of the literature was carried out. Five databases (PubMed, CINAHL, Web of Science, Cochrane Library, Google Scholar) were systematically explored with a time limit of five years. Included studies were assessed using Jadad Score and PEDro Scale. Results: Four RCTs were included in this systematic review. In all studies, multidisciplinary home care supported by technology were compared with in-person models. Remote care models were effective in managing pressure injury, infection, and muscle atrophy and improve quality of life. Conclusions: Remote care models can be a key tool for improving self-efficacy, decreasing hospitalizations and preventing long-term mortality. Full article

Spinal cord injury (SCI) triggers both local and systemic pathological responses that evolve over time and differ with injury severity. Small extracellular vesicles (sEVs), known mediators of intercellular communication, may serve as biomarkers reflecting these complex dynamics. In this study, we investigated whether SCI severity modulates the composition and abundance of circulating plasma-derived sEVs across subacute and chronic phases. Using a graded thoracic contusion model in mice, plasma was collected at defined timepoints post-injury. sEVs were isolated via size-exclusion chromatography and characterized using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and MACSPlex surface marker profiling. We observed an SCI-dependent increase in sEVs during the subacute (7 days) phase, most notably in moderate injuries (50 kdyne), with overall vesicle counts lower chronically (3 months). CD9 emerged as the predominant tetraspanin sEV marker, while CD63 and CD81 were generally present at low levels across all injury severities and timepoints. Surface sEV analysis revealed dynamic regulation of CD41⁺, CD44⁺, and CD61⁺ in the CD9⁺ sEV subset, suggesting persistent systemic signaling activity. These markers, traditionally associated with platelet function, may also reflect immune or reparative responses following SCI. Our findings highlight the evolving nature of sEV profiles after SCI and support their potential as non-invasive biomarkers for monitoring injury progression. Full article

Spinal cord injuries (SCI) often result in impaired motor functions. To quantify these impairments, swimming patterns were analyzed in individuals with SCI. Water provides a unique rehabilitation environment where buoyancy supports weight-bearing activities and can reveal deficits that might otherwise go unnoticed. Data were collected of 30 individuals with chronic, motor-incomplete SCI and 20 healthy controls during breaststroke swimming on a kickboard. Using eight wearable inertial sensors attached to the lower limbs, we captured detailed kinematic data. Spatiotemporal parameters were then calculated and compared between the two groups to assess differences in swimming patterns. An analysis of the parameters revealed significant differences in velocity (p < 0.001, ε² = 0.476) and distance per stroke (p < 0.001, ε² = 0.516), indicating decreased swimming speeds in individuals with SCI compared to controls. Furthermore, individuals with SCI demonstrated a reduced range of motion (RoM) in the ankle (p = 0.003, ε² = 0.516) and knee joints (p = 0.041, ε² = 0.142). The limited RoM likely contributes to the shorter distance covered per stroke. These observations underscore the impact of SCI on functional capabilities. The developed algorithm holds promise for enhancing the assessment of motor deficits after neurological injuries. Full article

Study Design: Pilot randomized clinical trial. Objective: To examine the effect of electrically evoked muscle hypertrophy on indices of spasticity, as measured by Biodex after spinal cord injury (SCI). Setting: Medical research center. Methods: Thirteen males with chronic SCI were randomized into sixteen weeks of either surface neuromuscular resistance training (NMES-RT) + testosterone treatment (TT) (n = 7) or a TT-only group (n = 6). A Biodex isokinetic dynamometer was used to measure knee extensor and flexor muscle spasticity at the beginning (baseline; BL) and at the end (post-intervention; PI) of 16 weeks. The passive tension of the right knee extensor and flexor muscle groups were evaluated at angles of 5°, 30°, 60°, 90°, 180°, and 270° per second (sec). Dual energy X-ray absorptiometry and magnetic resonance imaging were used to measure leg lean mass and thigh muscle cross-sectional areas (CSAs). Results: Robust muscle hypertrophy was noted in leg lean mass [11%, p = 0.023] as well as whole thigh [17%, p = 0.001] and knee extensor muscle [28%, p = 0.001] CSAs in the NMES-RT+TT compared to the TT-only group. There was no difference in extensor or flexor spasticity between the NMES-RT+TT or TT-only groups at different angular velocities following 16 weeks of intervention. Collapsing the extensor passive torques indicated an (24–28%) increase (p < 0.004) in response to angular velocities at BL and following PI measurements [180 deg/sec (23%; p = 0.03) and 270 deg/sec (32%; p = 0.009)] compared to 5 deg/sec. The extensor slope showed a non-significant (p > 0.05) decrease of 15–28% across all angular velocities. The catch-AB slopes were non-significantly lower in the TT-only group compared to the NMES-RT+TT at higher speeds [90 deg/sec and 270 deg/sec] and attained a trend towards lower passive torque at 180 deg/sec [180 deg/sec: 15.5%, p = 0.05]. Conclusions: Evoking skeletal muscle hypertrophy did not increase spasticity indices at different angular velocities following sixteen weeks of NMES-RT+TT or TT in persons with chronic SCI. Augmenting muscle hypertrophy is likely to attenuate the hyper reflexive slope of the extensor spasticity. The findings may suggest that evoking muscle hypertrophy following NMES-RT does not increase indices of spasticity after SCI. The clinical implications are highly important in managing spasticity after SCI. Full article

Neuropathic pain is a chronic disorder that arises from damaged or malfunctioning nerves. Hypersensitivity to stimuli, also known as hyperalgesia, can cause a person to experience pain from non-painful stimuli, termed allodynia. Cannabis-based medicines (CBMs) may provide new treatment options to manage neuropathic pain. A review of the relevant studies was conducted to evaluate the effectiveness of CBMs in treating neuropathic pain. Scientific literature was systematically searched from January 2003 to December 2024 using the Web of Science Core Collection, PubMed, and MEDLINE. A total of 22 randomized controlled trials (RCTs) were identified that considered the use of 1′,1′-dimethylheptyl-Δ⁸-tetrahydrocannabinol-11-oic acid (CT-3), Δ⁹-tetrahydrocannabinol (Δ⁹-THC), cannabidiol (CBD), combinations of Δ⁹-THC with CBD, and cannabidivarin for treatment of neuropathic pain. Significant reductions in pain were reported in 15 studies focused on the treatment of multiple sclerosis, spinal cord injuries, diabetic neuropathy, postherpetic neuralgia, HIV-associated sensory neuropathy, peripheral neuropathic pain, complex regional pain syndrome, chronic radicular neuropathic pain, and peripheral neuropathy of the lower extremities. These positive outcomes often adopted personalized and adjusted dosing strategies. By contrast, seven RCTs observed no significant pain relief compared to placebo, although some had minor improvements in secondary outcomes, such as mood and sleep. Collectively, CBM treatments may improve pain scores, but study limitations such as small sample sizes and study durations, high placebo response rates, and trial unblinding because of the psychoactive effects of cannabinoids all hinder data interpretation and the extrapolation to chronic pain conditions. Hence, future RCTs will need to have larger numbers and be more extended studies that explore optimal dosing and delivery methods and identify patient subgroups that are most likely to benefit. While CBMs show potential, their current use balances modest benefits against possible adverse effects and variable outcomes. Full article

Recruiting participants for clinical trials targeting specific populations, like patients with chronic motor complete spinal cord injuries (SCIs), is challenging. The RESTORES trial evaluated spinal cord stimulation (SCS) combined with robotic neurorehabilitation for motor recovery in this population. This feasibility study enrolled three participants to assess SCS implant safety, synergistic effects of SCS and robotic rehabilitation, and clinical outcomes. Key recruitment barriers included the small patient pool, stringent eligibility criteria, patient skepticism, and logistical and emotional challenges. Strategies to address these challenges encompassed multidisciplinary collaborations with clinical centers, SCI associations, and patient support groups, including pre-surgical counselling and transparent communication. A dedicated clinical research coordinator ensured ethical compliance, logistical support, and participant engagement. Travel reimbursements, family involvement, and peer advocacy fostered accessibility and trust. Of the 115 patients screened, only 3 met the strict eligibility criteria, due to high screening failure rates and participant apprehension. Peer testimonials and family support helped enhance motivation and adherence. Ethical safeguards, like a data safety monitoring board, ensured participant safety and transparency. The RESTORES trial underscores the complexity of recruiting for pioneering interventions while highlighting the importance of tailored, patient-centric strategies. Insights gained will inform future trials and contribute to advancing SCI rehabilitation, offering hope for enhanced neurological recovery and quality of life for individuals with chronic motor complete SCI. Full article

Spasticity is a common complication after spinal cord injury (SCI) that significantly diminishes quality of life and complicates daily management. As a hallmark of upper motor neuron lesions, spasticity emerges through a complex post-injury process involving the resolution of spinal shock, an imbalance between excitatory and inhibitory signaling, and maladaptive neuronal plasticity, leading to hyperreflexia and chronic spasticity. Severe spasticity frequently results in pain, sleep disturbances, and marked functional impairments. This review systematically integrates motor neuron alterations with corresponding muscle manifestations, providing a comprehensive analysis of the brain–spinal cord–muscle pathway in spasticity pathogenesis. Through an in-depth analysis of the pathological and physiological changes in motor neurons post-SCI, this review offers a novel perspective that unveils the intrinsic mechanisms underlying spasticity formation, thereby establishing a robust theoretical foundation for developing targeted therapeutic strategies. Full article

Background/Objectives: Rates of depression, anxiety, sleep disturbances, and chronic pain are higher in people with spinal cord injury (SCI) compared with able-bodied individuals. Passive heat therapy (PHT), which raises core body temperature, may be an accessible therapeutic intervention. The effects of PHT on mental health, sleep, and pain in persons with SCI are unknown. Methods: We performed a time-controlled pre–post intervention pilot study in which ten veterans with chronic SCI underwent an 8-week supervised PHT intervention to raise oral temperature by 1 °C each session. Outcome measures were the 5-item Mental Health Inventory, Epworth Sleepiness Scale, and International Spinal Cord Injury Pain Extended Data Sets version 1.0. Results: There were no adverse events related to the intervention and nine out of ten participants completed all their intervention sessions. There was a reduction in pain intensity (p = 0.039) upon completing the intervention (from a median (IQR) of 2.0 (0.0, 3.5) to 1.0 (0.0, 4.5) on a 0–10 scale). However, there were no improvements in self-reported mental health or sleep outcomes (p > 0.339). Conclusions: This pilot study suggests that supervised repeated passive heat therapy may confer benefits for chronic pain in veterans with chronic SCI. Follow-up studies with larger sample sizes and more extensive sets of chronic pain outcomes are needed to confirm these findings. Full article

Background/Objectives: Nutritional needs for people with chronic spinal cord injury (SCI) are inadequately addressed due to the lack of comprehensive evidence and scattered research. We established a consensus-based framework for addressing the nutritional needs of community-dwelling adults with chronic SCI who can ingest food orally. Methods: A web-based Delphi design was employed to ascertain an expert consensus. The Delphi panel consisted of physicians, registered dietitians (RDs), and researchers knowledgeable in SCI and nutrition. Informed by a literature review, 18 nutrition statements were rated by 15 panelists. The survey included statements about SCI-specific dietary energy assessments and macro- and micronutrients. Results: The response rate for the panel (N = 15) was 100%. Consensus levels, scores, stability levels, and response numbers were documented for each statement. The statements received consensus scores ranging from 4.14 to 8.13 on a 9-point Likert scale. Alternative expert comments and suggestions were also provided for each statement. Conclusion: Engaging a diverse panel of experts, the real-time Delphi process yielded expert-reviewed nutrition statements based on an extensive literature review and expert opinions. The rated statements contribute to the ongoing dialogue in SCI-specific nutrition, providing a practical resource for healthcare professionals working with adults with chronic SCI. Full article

Objectives: This systematic review with meta-analysis compared cardiometabolic syndrome (CMS) in adults with chronic (≥1 year) spinal cord injury (SCI) to non-SCI individuals (controls) and athletes, analyzing the effect of specific injury characteristics and exploring temporal and geographical trends. Methods: Ovid Medline, Embase, Cochrane, CINAHL, Scopus, and Web of Science were searched from inception to September 2024. Adults with chronic SCI were included based on observational and baseline data derived from experimental studies. Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields assessed quality. Weighted means with 95% bootstrapped confidence intervals (CI) were computed for risk stratification. Group differences were assessed using random effects meta-analysis, calculating weighted mean differences with 95% bootstrapped CI. Temporal and geographical trends were evaluated with linear regression based on sample-size-weighted distributions and relevant covariates. Results: Of 31,163 identified records, 471 studies were included (n ≤ 31,782 SCI participants). CMS was present in men with SCI, paraplegia, tetraplegia, and injuries above T6; men with complete SCI (AIS A); and men and women with motor-complete SCI (AIS A–B). Compared to controls, adults with SCI had a lower body mass index (BMI), higher total and visceral fat, and worse lipid and carbohydrate profiles, including increased insulin resistance (IR). Tetraplegia was associated with greater visceral fat, poorer glycemic control, and lower BMI, insulin sensitivity, high-density lipoprotein-cholesterol (HDL-C), and triglycerides than paraplegia. Motor-complete SCI had lower BMI, HDL-C, and fasting glucose than motor-incomplete injuries. Injuries above T6 had lower blood pressure and higher fasting insulin levels than those below T6. Athletes with SCI had a lower BMI, fat mass, and fasting glucose, and higher systolic blood pressure than non-athletes with SCI, but frequently presented with obesity and carbohydrate dysfunction. Temporal analysis revealed increasing obesity trends and improved systolic blood pressure, while other CMS risk factors remained unchanged. We also identified global variations in obesity, lipids, blood pressure, and carbohydrate patterns. Conclusions: With a large sample, we revealed a widespread cardiometabolic burden in chronic SCI, even among athletes. Specifically, obesity, IR, and hypoalphalipoproteinemia worsened with increasing injury severity, alongside rising obesity trends and geographic disparities in risk profiles. These patterns highlight the evolution of what was deemed an epidemic into a global cardiometabolic pandemic. Full article

Background/Objectives: After spinal cord injury (SCI), poor dorsiflexor control and involuntary plantar-flexor contraction impair walking. As whole-body vibration (WBV) improves voluntary muscle activation and modulates reflex excitability, it may improve ankle control. In this study, the dosage effects of WBV on walking speed, dorsiflexion, and spinal reflex excitability were examined. Methods: Sixteen people with chronic motor-incomplete SCI participated in this randomized sham-control wash-in study. Two weeks of sham stimulation (wash-in phase) were followed by either 2 weeks of eight repetitions (short bout) or sixteen repetitions of WBV (long bout; intervention phase) per session. Walking speed, ankle angle at mid-swing, and low-frequency depression of the soleus H-reflex were measured before and after the wash-in phase and before and after the intervention phase. Results: A significant dosage effect of WBV was not observed on any of the measures of interest. There were no between-phase or within-phase differences in ankle angle during the swing phase or in low-frequency depression. When dosage groups were pooled together, there was a significant change in walking speed during the intervention phase (mean = 0.04 m/s, standard deviation = 0.06, p = 0.02). There was not a significant correlation between overall change in walking speed and dorsiflexion angle or low-frequency depression during the study. Conclusions: Whole-body vibration did not have a dosage-dependent effect on dorsiflexion during the swing phase or on spinal reflex excitability. Future studies assessing the role of corticospinal tract (CST) descending drive on increased dorsiflexor ability and walking speed are warranted. Full article

Objective: This multicenter study compares outcomes of open thoracoabdominal aortic aneurysm (TAAA) repair in patients < 60 years with (n = 106), versus without (n = 167), hereditary aortopathy. Methods: We conducted a retrospective analysis of 273 consecutive open TAAA repairs (2000–2024) at two European centers. The primary endpoint was early outcome. We used a Kaplan–Meier curve to assess survival, and logistic regression to identify predictors. Results: Operative death rates were similar (hereditary: 13/106 [12.3%] vs. non-hereditary: 22/167 [13.2%], p = 0.83). Hereditary aortopathy patients were younger (median 42 vs. 54 years, p < 0.001) with lower BMI (24.1 vs. 28.4 kg/m², p < 0.001). Non-genetic patients had higher rates of chronic kidney insufficiency (58/167 (34.7%) vs. 14/106 (13.2%), p < 0.001), coronary artery disease (43/167 (25.7%) vs. 9/106 (8.5%), p < 0.001), and prior myocardial infarction (31/167 (18.6%) vs. 4/106 (3.8%), p < 0.001). Hereditary aortopathy patients suffered more often from post-dissection TAAA (68/106 [64.2%] vs. 44/167 [26.3%], p < 0.001) and prior aortic surgery (81/106 (76.4%) vs. 79/167 (47.3%), p < 0.001). Pulmonary complications (67.0% vs. 61.1%, p = 0.32), acute kidney injury (25.5% vs. 22.8%, p = 0.61), and spinal cord ischemia (6.6% vs. 10.2%, p = 0.31) were comparable between groups. Overall 5-year survival was 65.7%; the rate of any reintervention during follow up was 21.2%. Logistic regression identified no predictors for perioperative mortality. Conclusions: Open TAAA repair in patients < 60 years carries relevant perioperative mortality, which is comparable between hereditary and non-hereditary groups; non-hereditary patients had impaired preoperative cardiopulmonary status. Full article