Spinal Patients Research Articles

Time to Surgery Following Complete Cervical Spinal Cord Injury: Evolution of Clinical Practice Patterns Over a Decade from 2010 to 2020 Across North American Trauma Centers.

This study aims to quantify the change in time to surgery for treatment of complete traumatic cervical spinal cord injury (SCI) patients in American College of Surgeons accredited trauma centers across North America over the last decade (2010-2020). This multi-center retrospective observational cohort study used data from the Trauma Quality Improvement Program from 2010 to 2020. All surgically treated patients with complete traumatic cervical SCI were included. Primary outcome was time to spine surgery from treating hospital arrival in hours. Both descriptive statistics and a multi-variable Poisson regression model clustering standard of errors by each included trauma center were used to evaluate and quantify the annual change in time to surgical intervention. The study included 6855 complete traumatic cervical SCI patients managed across 484 trauma centers in North America. Median time to spine surgery was 14.6 h. A total of 4618 patients (67.3%) underwent surgical intervention within 24 h from hospital arrival. From 2010 to 2020, median time to surgery decreased by an average 0.6 h (±0.15) per year. A multi-variable adjusted model for time to surgery demonstrated a significant downward annual reduction of 5% in time to surgery between the years 2010 and 2020 (Incidence rate ratio = 0.95; 95% Confidence Interval: 0.93-0.96). This study provides compelling real-world based quantification of the change in time to surgical intervention following traumatic cervical SCI. A significant decreasing annual trend pertaining to surgical timing across trauma centers in North America over the past decade was demonstrated.

Enhanced inhibitory input to triceps brachii in humans with spinal cord injury.

Most individuals with cervical spinal cord injury (SCI) show increased muscle weakness in the elbow extensor compared to elbow flexor muscles. Although this is a well-known functional deficit, the underlying neural mechanisms remain poorly understood. To address this question, we measured the suppression of voluntary electromyographic activity (svEMG; a measurement thought to reflect changes in intracortical inhibition) by applying low-intensity transcranial magnetic stimulation over the arm representation of the primary motor cortex during 10% of isometric maximal voluntary contraction (MVC) into elbow flexion or extension in individuals with and without chronic cervical SCI. We found that the svEMG latency and duration were not different between the biceps and triceps brachii in controls but prolonged in the triceps in individuals with SCI. The svEMG area was larger in the triceps compared to the biceps in both groups and further increased in SCI participants, suggesting a pronounced intracortical inhibitory input during elbow extension. A negative correlation was found between svEMG area and MVCs indicating that control and SCI participants with lower svEMG area had larger MVCs. The svEMG area was not different between 5% and 30% of MVC, making it less probable that differences in muscle strength between groups contributed to our results. These findings support the existence of strong inhibitory input to corticospinal projections controlling elbow extensor compared to flexor muscles, which is more pronounced after chronic cervical SCI. KEY POINTS: After cervical spinal cord injury (SCI), people often recover function in elbow flexor, but much less in elbow extensor muscles. The neural mechanisms contributing to this difference remain unknown. We measured the suppression of voluntary electromyographic activity (svEMG) elicited through low-intensity transcranial magnetic stimulation of the primary motor cortex (assumed to reflect changes in intracortical inhibition) in the biceps and triceps muscles in controls and individuals with cervical chronic incomplete SCI. We found increased svEMG area in the triceps compared to the biceps in controls and SCI participants, with this measurement being even more pronounced in the triceps after SCI. The svEMG area correlated with maximal voluntary contraction values in both groups, suggesting the people with lesser inhibition had larger motor output. Our results support the presence of strong cortical inhibitory input to corticospinal projections controlling elbow extensor compared to elbow flexors muscles after cervical SCI.

Complete spinal cord injury due to acute non-traumatic cervical disc herniation and associated epidural haematoma: A case report.

A previously healthy 40-year-old woman experienced a sudden complete tetraplegia (C8, AIS-A). MRI revealed a C6/C7 disc herniation surrounded by an epidural haematoma. Physicians must recognize acute, non-traumatic disc herniation as a potential cause of spinal cord injury, urging prompt diagnosis and intervention.

Traumatic spinal cord injuries due to falls from trees in a tertiary rehabilitation center: a retrospective analysis of causes and outcomes

Aims: Falls from heights are a major cause of spinal cord injury. In developing countries such as Turkey, where fruit picking from trees is an important part of the agricultural economy, falls from trees are common. This study aims to comprehensively analyze the causes and consequences of spinal cord injuries due to falls from trees. Methods: This retrospective study reviewed cases of spinal cord injury resulting from falls from trees, treated at a tertiary rehabilitation center between March 2020 and November 2023. Data encompassed demographics (age, gender, occupation, education), spinal injury specifics (level, severity), additional injuries, tree fall details (type of tree, height of fall, cause of fall, safety precautions), and treatment details (surgery need, hospital stay duration). The patients who fell from trees were divided into two groups: those who fell from walnut trees and those who fell from other trees, and statistical analyses were performed accordingly. Results: Among the 49 patients falling from trees, the mean age was 52.3 ± 13.4 years, with 73.5% being male, 32 patients (%65.3) had graduated from primary or secondary school. No safety precautions were taken by any participants. Paraplegia (%87.8) and complete spinal cord injuries (57.1%) were common. Additional injuries occurred in %61.2 of cases. In terms of fall causes, the most common was branch breakage (%57.1), while walnut trees accounted for %44.9 of falls. There was a significant difference in education levels between the group that fell from walnut trees and the group that fell from other trees (p:0.028). Falls from walnut trees resulted in higher fall heights, complete injury rates, and longer hospital stays (p:0.003, p:0.047, p: 0.010). Conclusion: This study found that spinal cord injuries from falls often lead to additional injuries, with none of the patients taking safety precautions. This study found that walnut trees were the most common cause of spinal cord injury from falling trees. This study highlights the need for improved safety precautions and educational interventions.

Operative Timing in Cervical Spine Trauma.

Narrative review. To review existing literature regarding surgical timing in cervical trauma with a focus on acute traumatic central cord syndrome. Traumatic central cord syndrome is the most common incomplete spinal cord injury. Substantial basic science literature has proposed ischemic and secondary injury-driven mechanisms underpinning the urgency of operative intervention. However, only recently has a relative consensus emerged in the clinical literature regarding the safety, efficacy, and necessity of early operative intervention for acute traumatic central cord syndrome. A literature search was conducted of studies in PubMed Central and Cochrane Database related to timing in cervical spine trauma. Recently, several major systematic reviews and consensus statements have endorsed the importance and safety of early (<24h) operative decompression in the setting of traumatic spinal cord injury. Despite decades of conflicting data, a similar trend appears to be emerging for traumatic central cord syndrome. These clinical developments join a large body of basic science work regarding the importance of early decompressive surgery in relieving acute ischemic insult and minimizing the effects of secondary injury. However, further work is needed to delineate optimal surgical timing, especially regarding "ultra-early" (<8 h) protocols, and to aid in creating accelerated screening pathways.

Outcome of posterior decompression by L1 laminectomy, transpedicular fixation, posterolateral fusion in burst fracture L1 with incomplete spinal cord injury

Introduction: Burst fractures are more severe than compression fractures as the bones spread out in all directions and may damage the spinal cord, leading to paralysis or nerve injury. This study aims to find the surgical outcomes of Posterior Decompression by L1 Laminectomy in terms of burst fracture with incomplete spinal cord injury. Methods: 48 adult patients with burst fractures with incomplete spinal injury came to NITR from June 2023 to May 2024. In this non-randomized clinical trial, the outcomes of decompression by L1 laminectomy were analysed by using the canal encroachment ratio, while deformity correction was assessed using the sagittal Cobb angle and the percentage of anterior vertebral height for the treatment of L1 burst fracture with incomplete spinal cord injury. Results: The patients were followed up for an average of 12 months. The mean operation time was 154.53 minutes, mean intraoperative blood loss of 48.84 mL, and the mean incision length was 7.78 cm. The canal encroachment ratio decreased significantly, as well as the sagittal Cobb angle, and anterior vertebral percentage height increased. Oswestry Disability Index, and American Spinal Injury Association impairment scale classification were significant. Conclusions: Posterior decompression combined with Transpedicular Fixation and Posterolateral Fusion in the treatment of Burst Fracture L1 with Incomplete Spinal Cord Injury is safe and effective.

Pedal Reaction Forces and Electromyography Responses Indicate Eccentric Contractions During Motorized Cycling in a Rat Model of Incomplete Spinal Cord Injury.

Motorized cycling (MC) is utilized as an alternative to traditional exercise in individuals who are unable to perform voluntary movements post-spinal cord injury. Although rodent models of MC often show more positive outcomes when compared with clinical studies, the cause of this difference is unknown. We postulate that biomechanical differences between rats and humans may contribute to this discrepancy. To begin to test this theory, we examined pedal reaction forces and electromyography (EMG) of hindlimb muscles as a function of cycle phase and cadence in a rat model of MC. We found that higher cadences (≥30 RPM) increased EMG and force, with higher forces observed in animals with contusion injuries as compared with transections. To further investigate the forces, we developed a technique to separate rhythmic (developed with the motion of the pedals) from nonrhythmic forces. Rhythmic forces resulted from induced eccentric muscle contractions that increased (amplitude and prevalence) at higher cadences, whereas nonrhythmic forces showed the opposite pattern. Our results suggest that muscle activity during MC in rats depends on the stretch reflex, which, in turn, depends on the rate of muscle lengthening that is modulated by cadence. Additionally, we provide a framework for understanding MC that may help translate results from rat models to clinical use in the future.

Intermittent hypoxia enhances voluntary activation and reduces performance fatigability during repeated lower limb contractions.

Prior research has highlighted the therapeutic benefits of acute intermittent hypoxia (AIH) in enhancing motor performance after motor incomplete spinal cord injury and in able-bodied individuals. While studies in rodents and humans indicate that AIH may facilitate motor excitability, the relationship between excitability changes and functional performance remains unclear. Additionally, discrepancies in the effects of AIH on excitability in able-bodied individuals merit further investigation. Understanding the concurrent impact of repetitive AIH on voluntary activation and spinal reflex excitability may clarify the functional implications of AIH for muscle force production. High voluntary activation is vital for sustaining torque production during activities that require repeated muscle contractions. We hypothesized that repetitive AIH would attenuate declines in both voluntary activation and maximum torque production typically observed during fatiguing contractions. To test this hypothesis, we examined the effects of four consecutive days of AIH on voluntary activation and torque generation during repeated maximal plantar flexion contractions. We assessed changes in voluntary activation using the central activation ratio (CAR) by calculating the ratio of voluntary torque to the torque produced with supramaximal electrical stimulation. Consistent with our hypothesis, we show that repetitive AIH significantly increases both CAR and peak torque during fatiguing contractions. We did not observe any changes in resting spinal reflex excitability or antagonist muscle coactivation during the fatiguing contractions post-AIH. Together, these findings suggest that repetitive AIH reduces performance fatigability through enhanced descending neural drive. Optimizing voluntary activation is critical for facilitating the recovery of functional walking skills after neurological injury.

Dosing overground robotic gait training after spinal cord injury: a randomized clinical trial protocol

BackgroundRobotic exoskeletons have changed rehabilitation care available to people after spinal cord injury (SCI). Yet, the current evidence base is insufficient to identify the optimal dose and neurophysiological mechanism of robotic exoskeleton gait training (RGT) as an effective rehabilitation approach. This study will (1) examine whether the frequency of RGT after motor incomplete SCI impacts function and health outcomes, (2) analyze the neuroplastic effects of RGT dose, and (3) evaluate the safety, tolerability, and feasibility of delivering RGT.MethodsWe will enroll 144 participants with motor incomplete SCI admitted to inpatient rehabilitation within 6 months of SCI. Participants will be randomized based on injury severity and level into one of 3 RGT frequency groups (high, moderate, low) or none/usual care only. Participants will complete 24 RGT sessions and be assessed at admission and discharge to inpatient rehabilitation, post-RGT intervention, 1-month post-RGT, and 9-month post-SCI. Outcomes include Walking Index for Spinal Cord Injury-II, health outcomes (gait speed, Spinal Cord Independence Measure, pain, fatigue, spasticity, general health, quality of life, physical activity), and motor evoked potential amplitudes obtained using transcranial magnetic stimulation.DiscussionSuccessful completion of this study will provide an evidence-based intervention, specifically tailored to meet the unique needs of people with SCI, which supports walking recovery; maximizing health, function, and ultimately participation. The intervention will further support widespread clinical implementation of exoskeleton use during acute rehabilitation.Trial registrationClinicalTrials.gov NCT05218447. Registered on June 23, 2022.

EPIDEMIOLOGY OF SPINAL CORD INJURY AND ASSOCIATED MORTALITY, PAST AND PRESENT. IS THERE A DIFFERENCE?

The demographics of spinal cord injury population has been dynamic over time especially with aging. This study investigated the patterns of SCI admissions by age in the United States over the past decade. Data was evaluated (2010-21), from the National Spinal Cord Injury Model Systems records. Patients were compared based on age (<70 and ≥70 years). Analysis of mortality, neurologic level of injury, neurologic improvement, and mortality by ASIA grade and neurologic level of injury. Patients greater than 70 were defined as elderly. 8,137 patients were reviewed with mean age 42.6 years (range 15-88). The mean admission rate per year was 678 (range 378 -758). For the elderly vs the younger cohort, incidence of fall decreased by 5% vs 3.3%, vehicle accidents increased by 3% vs 14%, high tetraplegia increased by 14.7% vs 22.5%, low tetraplegia decreased by 12% vs 5.7%. In the elderly, ASIA grades A, B and C decreased significantly while ASIA Grade D increased by 23.8%. In the younger cohort ASIA A and B injuries increased while C and D increased, all <5%. Overall, 32.1% of those with ASIA A and 68% with ASIA B injuries improved within one to two years after injury. In-hospital and 1-year mortalities decreased by 14.5% and 35.4% respectively in the elderly. The incidence of SCI increased. High cervical and incomplete injuries increased, while complete spinal cord injuries declined. In-hospital and 1-year mortality decreased. There was recovery in select cases of complete spinal cord injuries within 1 year.

Feasibility and safety of two weeks of blood flow restriction exercise in individuals with spinal cord injury

Context Reduced muscle strength and function are common after spinal cord injury (SCI). While low-load blood flow restriction exercise (BFRE) enhances muscle strength in healthy and clinical populations, its safety and feasibility in individuals with SCI remain underexplored. Objectives To investigate the feasibility and safety of low-load BFRE in individuals with incomplete SCI. Study Design Case series. Setting SCI rehabilitation center. Participants Six participants with motor incomplete SCI were enrolled in the study. Intervention A two-week BFRE intervention for the lower limbs was conducted twice weekly at 40% total arterial occlusion pressure, using 30-40% of 1-repetition maximum loads. Outcome Measures Feasibility measures, specifically recruitment and eligibility rates and intervention acceptability, were collected. Blood pressure (BP) responses and specific coagulation markers for deep vein thrombosis (DVT) were assessed as safety measures. Results Recruitment and eligibility rates were 2.8% and 6.6% for individuals admitted for first-time rehabilitation (subacute SCI) and 8.3% and 13.9% for 4-week readmission rehabilitation stays (chronic SCI), respectively. Intervention acceptability was high, characterized by 95.8% training adherence and low-to-moderate self-reported pain levels. BP responses and changes in C-reactive protein, Fibrinogen, and D-dimer during the intervention remained within clinically acceptable levels. Conclusion BFRE was feasible in an SCI rehabilitation setting despite a low recruitment rate. BFRE imposed no heightened risk of DVT or severe BP fluctuations in the present case series. Additionally, no severe adverse events occurred, and only mild complaints were reported. More extensive safety considerations warrant larger-scale exploration. Trial registration ClinicalTrials.gov identifier: NCT03690700.

Acute Implantation of a Bioresorbable Polymer Scaffold in Patients With Complete Thoracic Spinal Cord Injury: A Randomized Controlled Trial (INSPIRE 2.0).

Traumatic spinal cord injury (SCI) remains a devastating condition with no proven effective treatment options available. In a prior single-arm study of patients with thoracic complete SCI (INSPIRE; ClinicalTrials.gov, NCT02138110), acute implantation of an investigational bioresorbable polymer scaffold (Neuro-Spinal Scaffold [NSS]) appeared to be safe through 24 months postimplantation and was associated with an American Spinal Injury Association Impairment Scale (AIS) conversion rate that exceeded historical controls. Here, we evaluated whether NSS implantation demonstrates probable benefit for safety and neurological recovery in patients with thoracic complete SCI vs standard-of-care spine surgery. INSPIRE 2.0 was a randomized, controlled, parallel, multicenter study conducted at Level I trauma centers in the United States (ClinicalTrials.gov, NCT03762655; funded by InVivo Therapeutics Corporation). Patients with AIS grade A, thoracic (T2-T12), nonpenetrating SCI requiring spine surgery ≤7 days postinjury were randomized (1:1, computer-generated allocation) to undergo NSS implantation or spine surgery alone (control group). Patients and follow-up International Standards for Neurological Classification of SCI assessors were blinded. A predefined study success criterion required the proportion of patients with improvement of ≥1 AIS grade at 6 months postsurgery (primary endpoint) to be ≥20% higher in the NSS group than in the control group. Target enrollment was reached (N = 20) with 10 patients randomized and analyzed in each group. At 6 months postsurgery, an improvement in the AIS grade was reported in 2 NSS patients (20%; both to AIS C) and 3 control group patients (30%; to AIS B [n = 2] or AIS C [n = 1]). No serious or unanticipated adverse device effects were reported. The study was closed to further follow-up because of not meeting its primary endpoint. In this small group of patients with thoracic complete (AIS A) SCI, implantation of an intraparenchymal bioresorbable scaffold did not produce probable clinical benefit. However, this study provides evidence that surgical intervention in an injured spinal cord parenchyma may be performed safely.

The Effect of Photobiomodulation on Bone Mineral Density, Serum Vitamin D, and Bone Formation Markers in Individuals with Complete Spinal Cord Injuries with Osteoporosis.

Study design: A quasi-experimental study utilized a matched-pair design, administering photobiomodulation at four-sites on one side of the body and assigning control to the other side at corresponding sites. Objectives: This study aimed to assess photobiomodulation treatment effects on bone mineral density (BMD) measurement using dual-energy X-ray-absorptiometry in individuals with complete spinal cord injury (C.SCI) and osteoporosis. Methods: Eight patients received treatment at four-sites: forearm-mid-distal (MID), proximal-femur, distal-femur, and proximal-tibia, totaling 32 sites. Using an 830 nm gallium-aluminum-arsenide semiconductor laser irradiation was administered three times weekly for 8 weeks. Different doses (energy density) were determined depending on bone depth from skin surface, as assessed by sonography and adjusted through irradiation time to be 8, 10, and 12 J/cm2 for depths <1 cm, between 1 and 1.5 cm, and >1.5 cm, respectively, using 200 mW power to deliver the optimal isodose of laser at each depth of bone within each therapeutic site. BMD was measured at baseline, week 8 of treatment, and week 15 of follow-up. Serum 25-(OH)-vitamin D and bone formation markers including osteocalcin and bone-alkaline-phosphatase (B-ALP) were also assessed at baseline and week 8 of treatment. Results: Significant increases in BMD were noted in proximal-femur and forearm-MID at both week 8 and week 15. Serum 25-(OH)-vitamin D levels significantly increased after treatment. However, no notable changes were observed in distal-femur and proximal-tibia BMD or in osteocalcin and B-ALP levels. Conclusions: Photobiomodulation (830 nm) laser demonstrated efficacy in improving BMD at proximal-femur and forearm-MID in individuals with C.SCI. Moreover, the observed positive influence on vitamin D levels suggests a potential photobiomodulation role, warranting further investigation.

Clinical Risk Factors Associated with the Need for Tracheostomy in Traumatic Cervical and High Thoracic Spinal Cord Injury

BackgroundOur objective was to assess the association of completeness and level of spinal cord injury (SCI) with the need for tracheostomy and identify additional risk factors predictive of tracheostomy. MethodsThis was a retrospective review of patients with SCI between January 2017 and December 2022. ResultsPatients with complete SCI were roughly thirty-three times more likely to have a tracheostomy when compared to incomplete injury (82% vs 12%, p<0.001, OR = 32.9). The rate of tracheostomy did not differ between spinal cord levels for complete (p=0.68) or incomplete (p=0.08) injuries. Penetrating injury, low GCS, high ISS, and polytrauma were associated with tracheostomy need in incomplete SCI. ConclusionComplete injury was statistically significantly associated with the need for tracheostomy while level of injury failed to reach significance. Patients with incomplete SCI that have certain clinical risk factors should be considered for early tracheostomy.

Metabolic Cost Of Underwater Treadmill Exercise Among Individuals With Incomplete Spinal Cord Injury

Metabolic Cost Of Underwater Treadmill Exercise Among Individuals With Incomplete Spinal Cord Injury

Effect Of Supraspinal Input On Muscle Activation During Assisted Leg Cycling After Complete Spinal Cord Injury

Effect Of Supraspinal Input On Muscle Activation During Assisted Leg Cycling After Complete Spinal Cord Injury

Enhanced spinal cord repair using bioengineered induced pluripotent stem cell-derived exosomes loaded with miRNA

BackgroundA spinal cord injury (SCI) can result in severe impairment and fatality as well as significant motor and sensory abnormalities. Exosomes produced from IPSCs have demonstrated therapeutic promise for accelerating spinal cord injury recovery, according to a recent study.ObjectiveThis study aims to develop engineered IPSCs-derived exosomes (iPSCs-Exo) capable of targeting and supporting neurons, and to assess their therapeutic potential in accelerating recovery from spinal cord injury (SCI).MethodsiPSCs-Exo were characterized using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and western blot. To enhance neuronal targeting, iPSCs-Exo were bioengineered, and their uptake by neurons was visualized using PKH26 labeling and fluorescence microscopy. In vitro, the anti-inflammatory effects of miRNA-loaded engineered iPSCs-Exo were evaluated by exposing neurons to LPS and IFN-γ. In vivo, biodistribution of engineered iPSC-Exo was monitored using a vivo imaging system. The therapeutic efficacy of miRNA-loaded engineered iPSC-Exo in a SCI mouse model was assessed by Basso Mouse Scale (BMS) scores, H&E, and Luxol Fast Blue (LFB) staining.ResultsThe results showed that engineered iPSC-Exo loaded with miRNA promoted the spinal cord injure recovery. Thorough safety assessments using H&E staining on major organs revealed no evidence of systemic toxicity, with normal organ histology and biochemistry profiles following engineered iPSC-Exo administration.ConclusionThese results suggest that modified iPSC-derived exosomes loaded with miRNA have great potential as a cutting-edge therapeutic approach to improve spinal cord injury recovery. The observed negligible systemic toxicity further underscores their potential safety and efficacy in clinical applications.

Traumatic Central Cord Syndrome.

Central cord syndrome (CCS) is the most common form of incomplete spinal cord injury, with an increasing incidence with the aging population. This is a clinical diagnosis defined by weakness greater in the upper than lower extremities and often prominent sensory complaints in the hands. CCS is typically seen in individuals with underlying cervical canal stenosis from spondylosis who experience sudden forceful movement of the neck, especially hyperextension, resulting in contusion of the spinal cord. The prognosis in CCS is relatively favorable with improvement in neurological deficits, except for fine motor control of the hands. Neuropathic pain may persist even in those with excellent motor recovery. Nonoperative management may be appropriate in selected patients, but surgery is usually necessary in those with poor neurological recovery or further deterioration. The optimal timing of surgical intervention has not been defined, but recent evidence suggests that early surgery (≤24h) may lead to greater neurological recovery, shorter hospital stay, and fewer inpatient complications. Management in any given patient must be considered in the context of the anatomy and location of spinal cord compression, the presence of fractures or ligamentous instability, the temporal course of signs and symptoms, as well as the patient's overall health.

Changes in intra- and interlimb reflexes from forelimb cutaneous afferents after staggered thoracic lateral hemisections during locomotion in cats.

In quadrupeds, such as cats, cutaneous afferents from the forepaw dorsum signal external perturbations and send inputs to spinal circuits to co-ordinate the activity in muscles of all four limbs. How these cutaneous reflex pathways from forelimb afferents are reorganized after an incomplete spinal cord injury is not clear. Using a staggered thoracic lateral hemisections paradigm, we investigated changes in intralimb and interlimb reflex pathways by electrically stimulating the left and right superficial radial nerves in seven adult cats and recording reflex responses in five forelimb and ten hindlimb muscles. After the first (right T5-T6) and second (left T10-T11) hemisections, forelimb-hindlimb co-ordination was altered and weakened. After the second hemisection, cats required balance assistance to perform quadrupedal locomotion. Short-, mid- and long-latency homonymous and crossed reflex responses in forelimb muscles and their phase modulation remained largely unaffected after staggered hemisections. The occurrence of homolateral and diagonal mid- and long-latency responses in hindlimb muscles evoked with left and right superficial radial nerve stimulation was significantly reduced at the first time point after the first hemisection, but partially recovered at the second time point with left superficial radial nerve stimulation. These responses were lost or reduced after the second hemisection. When present, all reflex responses, including homolateral and diagonal, maintained their phase-dependent modulation. Therefore, our results show a considerable loss in cutaneous reflex transmission from cervical to lumbar levels after incomplete spinal cord injury, albeit with preservation of phase modulation, probably affecting functional responses to external perturbations. KEY POINTS: Cutaneous afferent inputs co-ordinate muscle activity in the four limbs during locomotion when the forepaw dorsum contacts an obstacle. Thoracic spinal cord injury disrupts communication between spinal locomotor centres located at cervical and lumbar levels, impairing balance and limb co-ordination. We investigated cutaneous reflexes from forelimb afferents during quadrupedal locomotion by electrically stimulating the superficial radial nerve bilaterally, before and after staggered lateral thoracic hemisections in cats. We showed a loss/reduction of mid- and long-latency homolateral and diagonal reflex responses in hindlimb muscles early after the first hemisection that partially recovered with left superficial radial nerve stimulation, before being reduced after the second hemisection. Targeting cutaneous reflex pathways from forelimb afferents projecting to the four limbs could help develop therapeutic approaches aimed at restoring transmission in ascending and descending spinal pathways.

Distinct Genomic Expression Signatures after Low-Force Electrically Induced Exercises in Persons with Spinal Cord Injury.

People with a spinal cord injury are at an increased risk of metabolic dysfunction due to skeletal muscle atrophy and the transition of paralyzed muscle to a glycolytic, insulin-resistant phenotype. Providing doses of exercise through electrical muscle stimulation may provide a therapeutic intervention to help restore metabolic function for people with a spinal cord injury, but high-frequency and high-force electrically induced muscle contractions increase fracture risk for the underlying osteoporotic skeletal system. Therefore, we investigated the acute molecular responses after a session of either a 3 Hz or 1 Hz electrically induced exercise program. Ten people with a complete spinal cord injury completed a 1 h (3 Hz) or 3 h (1 Hz) unilateral electrically induced exercise session prior to a skeletal muscle biopsy of the vastus lateralis. The number of pulses was held constant. Tissue samples were analyzed for genomic and epigenomic expression profiles. There was a strong acute response after the 3 Hz exercise leading to the upregulation of early response genes (NR4A3, PGC-1α, ABRA, IRS2, EGR1, ANKRD1, and MYC), which have prominent roles in regulating molecular pathways that control mitochondrial biogenesis, contractile protein synthesis, and metabolism. Additionally, these genes, and others, contributed to the enrichment of pathways associated with signal transduction, cellular response to stimuli, gene expression, and metabolism. While there were similar trends observed after the 1 Hz exercise, the magnitude of gene expression changes did not reach our significance thresholds, despite a constant number of stimuli delivered. There were also no robust acute changes in muscle methylation after either form of exercise. Taken together, this study supports that a dose of low-force electrically induced exercise for 1 h using a 3 Hz stimulation frequency is suitable to trigger an acute genomic response in people with chronic paralysis, consistent with an expression signature thought to improve the metabolic and contractile phenotype of paralyzed muscle, if performed on a regular basis.