Spinal Patients Research Articles

Safety and potential effects of intrathecal injection of allogeneic human umbilical cord mesenchymal stem cell-derived exosomes in complete subacute spinal cord injury: a first-in-human, single-arm, open-label, phase I clinical trial

ObjectiveNeurological and functional impairments are commonly observed in individuals with spinal cord injury (SCI) due to insufficient regeneration of damaged axons. Exosomes play a crucial role in the paracrine effects of mesenchymal stem cells (MSCs) and have emerged as a promising therapeutic approach for SCI. Thus, this study aimed to evaluate the safety and potential effects of intrathecal administration of allogeneic exosomes derived from human umbilical cord MSCs (HUC-MSCs) in patients with complete subacute SCI.MethodsThis study was a single-arm, open-label, phase I clinical trial with a 12-month follow-up period. HUC-MSCs were extracted from human umbilical cord tissue, and exosomes were isolated via ultracentrifugation. After intrathecal injection, each participant a underwent complete evaluation, including neurological assessment using the American Spinal Injury Association (ASIA) scale, functional assessment using the Spinal Cord Independence Measure (SCIM-III), neurogenic bowel dysfunction (NBD) assessment using the NBD score, modified Ashworth scale (MAS), and lower urinary tract function questionnaire.ResultsNine patients with complete subacute SCI were recruited. The intrathecal injection of allogeneic HUC-MSCs-exosomes was safe and well tolerated. No early or late adverse event (AE) attributable to the study intervention was observed. Significant improvements in ASIA pinprick (P-value = 0.039) and light touch (P-value = 0.038) scores, SCIM III total score (P-value = 0.027), and NBD score (P-value = 0.042) were also observed at 12-month after the injection compared with baseline.ConclusionsThis study demonstrated that intrathecal administration of allogeneic HUC-MSCs-exosomes is safe in patients with subacute SCI. Moreover, it seems that this therapy might be associated with potential clinical and functional improvements in these patients. In this regard, future larger phase II/III clinical trials with adequate power are highly required.Trial registrationIranian Registry of Clinical Trials, IRCT20200502047277N1. Registered 2 October 2020, https://en.irct.ir/trial/48765.

Effectiveness of virtual-walking intervention combined with exercise on improving pain and function in incomplete spinal cord injury: a feasibility study.

A feasibility pilot study. To assess the feasibility a full-scale Randomized Controlled Trial aimed at assessing the beneficial effect of a Virtual Walking (VW)-based (Experimental intervention (EI)) on neuropathic pain and functionality in people with incomplete spinal cord injury (SCI). A hospital service (Hospital Universitario y Politécnico La Fe) and disability associations (TetraSport, CODIFIVA and ASPAYM). Twelve people with chronic incomplete SCI were randomized to EI (VW plus therapeutic exercise program (TE)) -or Control Intervention (CI (placebo VW and TE)) groups. A six-week intervention (3 sessions/week) was carried out. To assess feasibility, the following outcomes were used: level of restriction and validity of inclusion and exclusion criteria, participants' compliance, accessibility and acceptability of the intervention for participants, adequate pre-training time of physiotherapists. To explore therapy effectiveness, pain severity, and interference, mean and maximum isometric strength, walking speed, and walking ability were assessed before (Time 1, T1) and after (Time 2, T2) the intervention. 20% of the participants initially recruited did not meet inclusion criteria. In addition, all participants completed at least 80% of the intervention sessions and none of the participants dropped out before T2. No serious adverse event was found. Moreover, 91.67% of participants were willing to perform the intervention again and all therapists involved were adequately pre-trained. Finally, our preliminary results suggest that the proposed EI is effective. A full-scale RCT is feasible and preliminary results suggest that VW with TE could have a beneficial impact on pain and functionality in this population.

The LINGO-1-deficient neural stem cell-derived neural tissueoid showed enhanced retention and neuronal relay in the transected spinal cord

Neural stem cell (NSC)-derived neural tissueoids are a promising option to model spinal cord development and repair; however, the survival and integration ability with the host in vivo need to be improved. We aimed to determine if genetically engineered neural tissueoids in a NT-3 delivery scaffold exhibited increased retention and relay properties and to explore the underlying mechanisms. Gene expression screening of tissue and single-nucleus RNA sequencing revealed that leucine rich repeat and immunoglobin-like domain-containing protein 1 (LINGO-1) was significantly increased in neurons following spinal cord injury. The LINGO-1 protein accelerated cell death by increasing cleaved caspase-3 and interacting with TrkC to decrease NT-3-mediated phosphorylation of the PI3K/AKT/CREB axis, resulting in synaptic degradation. Subsequently, we seeded LINGO-1-deficient NSCs on a NT-3 delivery scaffold to construct an apoptosis resistant neural tissueoids, which was transplanted into a T9 complete spinal cord injury (SCI) rat model. The LINGO-1-deficient neural tissueoid was retained in the graft area, dramatically facilitated ascending and descending nerve fiber regeneration and connection, restored relay from brain to the caudal spinal cord, and improved the hindlimb movement function. This study demonstrates that transplantation of a LINGO-1-deficient tissueoid is an efficient pro-survival and neurogenesis strategy for the treatment of SCI.

Repetitive Transcranial Magnetic Stimulation with Body Weight-supported Treadmill Training Enhances Independent Walking of Individuals with Chronic Incomplete Spinal Cord Injury: A Pilot Randomized Clinical Trial.

The purpose of this study is to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with body weight-support treadmill training (BWSTT) for improving walking function of individuals with chronic incomplete spinal cord injury (iSCI). A 4-week, double-blinded, randomized, sham-controlled pilot study involved 12 sessions of real (10Hz, 1800 pulses) or sham rTMS combined with BWSTT (15-20min, moderate intensity). Walking independence was assessed using the Walking Index for Spinal Cord Injury II (WISCI-II). Lower extremity motor function (lower extremity motor score [LEMS]) and spasticity, sensory function, functional independence (Spinal Cord Injury Measure III [SCIM-III]), and quality of life were also assessed. Walking independence (WISCI-II) after the 6th session was higher in the BWSTT/rTMS real (n = 7) (median change (IQR): 3 (1.5 to 3.5)) than in the sham group (n = 8) (median change (IQR): 0 (0 to 0.25), but there was no difference between groups after 12th session (BWSTT/rTMS real median change (IQR): 4 (2 to 5); BWSSTT/rTMS sham median change (IQR): 0 (0 to 3.25). Compared to baseline, LEMS and SCIM-III mobility scores were increased after 12 sessions in the BWSTT/rTMS real but not in the sham group. Within- and between-group sensory function, functional independence, and quality of life remained similar. This preliminary result suggests that combining BWSTT with rTMS could lead to earlier gait improvement in patients with chronic iSCI.

Intraspinal microstimulation of the ventral horn has therapeutically relevant cross-modal effects on nociception.

Electrical stimulation of spinal networks below a spinal cord injury is a promising approach to restore functions compromised by inadequate and/or inappropriate neural drive. The most translationally successful examples are paradigms intended to increase neural transmission in weakened yet spared descending motor pathways and spinal motoneurons rendered dormant after being severed from their inputs by lesion. Less well understood is whether spinal stimulation is also capable of reducing neural transmission in pathways made pathologically overactive by spinal cord injury. Debilitating spasms, spasticity and neuropathic pain are all common manifestations of hyperexcitable spinal responses to sensory feedback. Whereas spasms and spasticity can often be managed pharmacologically, spinal cord injury-related neuropathic pain is notoriously medically refractory. Interestingly, however, spinal stimulation is a clinically available option for ameliorating neuropathic pain arising from aetiologies other than spinal cord injury, and the limited evidence available to date suggests that it holds considerable promise for reducing spinal cord injury-related neuropathic pain, as well. Spinal stimulation for pain amelioration has traditionally been assumed to modulate sensorimotor networks overlapping with those engaged by spinal stimulation for rehabilitation of movement impairments. Thus, we hypothesize that spinal stimulation intended to increase the ability to move voluntarily may simultaneously reduce transmission in spinal pain pathways. To test this hypothesis, we coupled a rat model of incomplete thoracic spinal cord injury, which results in moderate to severe bilateral movement impairments and spinal cord injury-related neuropathic pain, with in vivo electrophysiological measures of neural transmission in networks of spinal neurons integral to the development and persistence of the neuropathic pain state. We find that when intraspinal microstimulation is delivered to the ventral horn with the intent of enhancing voluntary movement, transmission through nociceptive specific and wide dynamic range neurons is significantly depressed in response to pain-related sensory feedback. By comparison, spinal responsiveness to non-pain-related sensory feedback is largely preserved. These results suggest that spinal stimulation paradigms could be intentionally designed to afford multi-modal therapeutic benefits, directly addressing the diverse, intersectional rehabilitation goals of people living with spinal cord injury.

Spinal cord injury in high-risk complex adult spinal deformity surgery: review of incidence and outcomes from the Scoli-RISK-1 study

Study designClinical case series.ObjectiveTo describe the cause, treatment and outcome of 6 cases of perioperative spinal cord injury (SCI) in high-risk adult deformity surgery.SettingAdult spinal deformity patients were enrolled in the multi-center Scoli-RISK-1 cohort study.MethodsA total of 272 patients who underwent complex adult deformity surgery were enrolled in the prospective, multi-center Scoli-RISK-1 cohort study. Clinical follow up data were available up to a maximum of 2 years after index surgery. Cases of perioperative SCI were identified and an extensive case review was performed.ResultsSix individuals with SCI were identified from the Scoli-RISK-1 database (2.2%). Two cases occurred intraoperatively and four cases occurred postoperatively. The first case was an incomplete SCI due to a direct intraoperative insult and was treated postoperatively with Riluzole. The second SCI case was caused by a compression injury due to overcorrection of the deformity. Three cases of incomplete SCI occurred; one case of postoperative hematoma, one case of proximal junctional kyphosis (PJK) and one case of adjacent segment disc herniation. All cases of post-operative incomplete SCI were managed with revision decompression and resulted in excellent clinical recovery. One case of incomplete SCI resulted from infection and PJK. The patient’s treatment was complicated by a delay in revision and the patient suffered persistent neurological deficits up to six weeks following the onset of SCI.ConclusionDespite the low incidence in high-risk adult deformity surgeries, perioperative SCI can result in devastating consequences. Thus, appropriate postoperative care, follow up and timely management of SCI are essential.

Insurance-Related Disparities in Withdrawal of Life Support and Mortality After Spinal Cord Injury

Identifying disparities in health outcomes related to modifiable patient factors can improve patient care. To compare likelihood of withdrawal of life-supporting treatment (WLST) and mortality in patients with complete cervical spinal cord injury (SCI) with different types of insurance. This retrospective cohort study collected data between 2013 and 2020 from 498 trauma centers participating in the Trauma Quality Improvement Program. Participants included adult patients (older than 16 years) with complete cervical SCI. Data were analyzed from November 1, 2023, through May 18, 2024. Uninsured or public insurance compared with private insurance. Coprimary outcomes were WLST and mortality. The adjusted odds ratio (aOR) of each outcome was estimated using hierarchical logistic regression. Propensity score matching was used as an alternative analysis to compare public and privately insured patients. Process of care outcomes, including the occurrence of a hospital complication and length of stay, were compared between matched patients. The study included 8421 patients with complete cervical SCI treated across 498 trauma centers (mean [SD] age, 49.1 [20.2] years; 6742 male [80.1%]). Among the 3524 patients with private insurance, 503 had WLST (14.3%) and 756 died (21.5%). Among the 3957 patients with public insurance, 906 had WLST (22.2%) and 1209 died (30.6%). Among the 940 uninsured patients, 156 had WLST (16.6%) and 318 died (33.8%). A significant difference was found between uninsured and privately insured patients in the adjusted odds of WLST (aOR, 1.49; 95% CI, 1.11-2.01) and mortality (aOR, 1.98; 95% CI, 1.50-2.60). Similar results were found in subgroup analyses. Matched public compared with private insurance patients were found to have significantly greater odds of hospital complications (odds ratio, 1.27; 95% CI, 1.14-1.42) and longer hospital stay (mean difference 5.90 days; 95% CI, 4.64-7.20), which was redemonstrated on subgroup analyses. Health insurance type was associated with significant differences in the odds of WLST, mortality, hospital complications, and days in hospital among patients with complete cervical SCI in this study. Future work is needed to incorporate patient perspectives and identify strategies to close the quality gap for the large number of patients without private insurance.

Utilization and timing of surgical intervention for central cord syndrome in the United States.

Retrospective cohort analysis. CCS is the most common type of incomplete spinal cord injury and can occur without or with bony injury. Surgical intervention and its timing for patients diagnosed with CCS has been controversial. The current study assessed utilization of and factors associated with operative intervention and its timing in patients diagnosed with central cord syndrome (CCS) in the absence of bony injury. Adult patients diagnosed with CCS in the absence of vertebral fracture were queried from the national, multi-insurance, administrative 2015-2020 M151 PearlDiver database. The incidence, trends, and timing of operative intervention following CCS were assessed. Patient characteristics associated with surgical intervention and its timing were determined. From 2015 to 2020, 11,653 patients meeting inclusion criteria were identified, of which surgical intervention was identified for 2,003 (17.2%) and thus nonsurgical intervention for 9,650 (82.8%). The proportion of patients undergoing operative intervention evolved from 11.5% in 2015 to 19.7% in 2020 (p < 0.0001). Of those undergoing surgical intervention, the greatest increase was seen for those undergoing surgery within two days of diagnosis (5.5% in 2015 to 12.3% in 2020, p < 0.0001). On multivariable analysis, more recent year of service, region of service, younger age, and higher comorbidity burden were independent predictors of operative management (p < 0.05 for all). The majority of a large cohort of patients with first diagnosis CCS in the absence of bony injury were managed non-operatively. Operative management increased over the years of study, were performed earlier after diagnosis, and varied based on patient characteristic and geographic region.

Amplify Gait to Improve Locomotor Engagement in Spinal Cord Injury (AGILE SCI) trial: study protocol for an assessor blinded randomized controlled trial

BackgroundAmong ambulatory people with incomplete spinal cord injury (iSCI), balance deficits are a primary factor limiting participation in walking activities. There is broad recognition that effective interventions are needed to enhance walking balance following iSCI. Interventions that amplify self-generated movements (e.g., error augmentation) can accelerate motor learning by intensifying sensorimotor feedback and facilitating exploration of motor control strategies. These features may be beneficial for retraining walking balance after iSCI. We have developed a cable-driven robot that creates a movement amplification environment during treadmill walking. The robot applies a continuous, laterally-directed, force to the pelvis that is proportional in magnitude to real-time lateral velocity. Our purpose is to investigate the effects of locomotor training in this movement amplification environment on walking balance. We hypothesize that for ambulatory people with iSCI, locomotor training in a movement amplification environment will be more effective for improving walking balance and participation in walking activities than locomotor training in a natural environment (no applied external forces).MethodsWe are conducting a two-arm parallel-assignment intervention. We will enroll 36 ambulatory participants with chronic iSCI. Participants will be randomized into either a control or experimental group. Each group will receive 20 locomotor training sessions. Training will be performed in either a traditional treadmill environment (control) or in a movement amplification environment (experimental). We will assess changes using measures that span the International Classification of Functioning, Disability and Health (ICF) framework including 1) clinical outcome measures of gait, balance, and quality of life, 2) biomechanical assessments of walking balance, and 3) participation in walking activities quantified by number of steps taken per day.DiscussionTraining walking balance in people with iSCI by amplifying the individual’s own movement during walking is a radical departure from current practice and may result in new strategies for addressing balance impairments. Knowledge gained from this study will expand our understanding of how people with iSCI improve walking balance and how an intervention targeting walking balance affects participation in walking activities. Successful outcomes could motivate development of clinically feasible tools to replicate the movement amplification environment within clinical settings.Trial registrationNCT04340063.

Distinct brain network patterns in complete and incomplete spinal cord injury patients based on graph theory analysis.

To compare the changes in brain network topological properties and structure-function coupling in patients with complete spinal cord injury (CSCI) and incomplete spinal cord injury (ICSCI), to unveil the potential neurobiological mechanisms underlying the different effects of CSCI and ICSCI on brain networks and identify objective neurobiological markers to differentiate between CSCI and ICSCI patients. Thirty-five SCI patients (20 CSCI and 15 ICSCI) and 32 healthy controls (HCs) were included in the study. Here, networks were constructed using resting-state functional magnetic resonance imaging to analyze functional connectivity (FC) and diffusion tensor imaging for structural connectivity (SC). Then, graph theory analysis was used to examine SC and FC networks, as well as to estimate SC-FC coupling values. Compared with HCs, CSCI patients showed increased path length (Lp), decreased global efficiency (Eg), and local efficiency (Eloc) in SC. For FC, ICSCI patients exhibited increased small-worldness, clustering coefficient (Cp), normalized clustering coefficient, and Eloc. Also, ICSCI patients showed increased Cp and Eloc than CSCI patients. Additionally, ICSCI patients had reduced SC-FC coupling values compared to HCs. Moreover, in CSCI patients, the SC network's Lp and Eg values were significantly correlated with motor scores, while in ICSCI patients, the FC network's Cp, Eloc, and SC-FC coupling values were related to sensory/motor scores. These results suggest that CSCI patients are characterized by decreased efficiency in the SC network, while ICSCI patients are distinguished by increased local connections and SC-FC decoupling. Moreover, the differences in network metrics between CSCI and ICSCI patients could serve as objective biological markers, providing a basis for diagnosis and treatment strategies.

Calcium homeostasis restoration in pyramidal neurons through micrometer-scale wireless electrical stimulation in spinal cord injured mice

Spinal Cord Injury (SCI) is a significant neurological disorder that can result in severe motor and cognitive impairments. Neuronal regeneration and functional recovery are critical aspects of SCI treatment, with calcium signaling being a crucial indicator of neuronal excitability. In this study, we utilized a murine model to investigate the effects of targeted wireless electrical stimulation (ES) on neuronal activity following SCI. After establishing a complete SCI model in normal mice, flexible electrodes were implanted, and targeted wireless ES was administered to the injury site. We employed fiber-optic photometric in vivo calcium imaging to monitor calcium signals in pyramidal neurons within the CA3 region of the hippocampus and the M1 region of the primary motor cortex. The experimental results demonstrated a significant reduction in calcium signals in CA3 and M1 pyramidal neurons following SCI (reduced by 76 % and 59 %, in peak respectively). However, the application of targeted wireless ES led to a marked increase in calcium signals in these neurons (increased by 118 % and 69 %, in peak respectively), indicating a recovery of calcium activity. These observations suggest that wireless ES has a positive modulatory effect on the excitability of pyramidal neurons post-SCI. Understanding these mechanisms is crucial for developing therapeutic strategies aimed at enhancing neuronal recovery and functional restoration following spinal cord injuries.

Enhancing balance and mobility in incomplete spinal cord injury with an overground gait trainer.

Prospective intervention study. The study aimed to assess the effect of Andago on balance, overground walking speed, independence levels, fear of falling, and quality of life in patients with acute motor incomplete Spinal Cord Injury. The study was conducted in Ankara/Türkiye. Five participants, classified as AIS D, underwent an eight-week treatment regimen, including three days a week of Andago-assisted walking and balance exercises, supplemented by two days a week of 40-minute sessions of conventional in-bed exercises. Berg Balance Scale scores increased significantly by 129% (p = 0.043). Overground walking speed calculated from 10MWT improved by 33% (p = 0.042). WISCI II levels improved significantly compared to baseline scores (p = 0.041). In the mobility subscale of SCIM III, the total SCIM III scores increased significantly (p = 0.042, p = 0.043, respectively). However, there was no significant improvement in WHOQOL-BREF scores (p = 0.080). The use of Andago facilitated functional progress in patients with acute incomplete SCI, emphasizing the importance of challenging balance and walking activities in triggering motor learning.

Multi-parametric MRI Assessment of Morpho-Functional Muscle Changes Following a 6-Months FES-cycling Training: A Pilot Study in People with Complete Spinal Cord Injury (Preprint)

Multi-parametric MRI Assessment of Morpho-Functional Muscle Changes Following a 6-Months FES-cycling Training: A Pilot Study in People with Complete Spinal Cord Injury (Preprint)

Acute intermittent hypoxia increases maximal motor unit discharge rates in people with chronic incomplete spinal cord injury.

Acute intermittent hypoxia (AIH) is an emerging technique for enhancing neuroplasticity and motor function in respiratory and limb musculature. Thus far, AIH-induced improvements in strength have been reported for upper and lower limb muscles after chronic incomplete cervical spinal cord injury (iSCI), but the underlying mechanisms have been elusive. We used high-density surface EMG (HDsEMG) to determine if motor unit discharge behaviour is altered after 15×60s exposures to 9% inspired oxygen, interspersed with 21% inspired oxygen (AIH), compared to breathing only 21% air (SHAM). We recorded HDsEMG from the biceps and triceps brachii of seven individuals with iSCI during maximal elbow flexion and extension contractions, and motor unit spike trains were identified using convolutive blind source separation. After AIH, elbow flexion and extension torque increased by 54% and 59% from baseline (P=0.003), respectively, whereas there was no change after SHAM. Across muscles, motor unit discharge rates increased by ∼4 pulses per second (P=0.002) during maximal efforts, from before to after AIH. These results suggest that excitability and/or activation of spinal motoneurons is augmented after AIH, providing a mechanism to explain AIH-induced increases in voluntary strength. Pending validation, AIH may be helpful in conjunction with other therapies to enhance rehabilitation outcomes after incomplete spinal cord injury, due to these enhancements in motor unit function and strength. KEY POINTS: Acute intermittent hypoxia (AIH) causes increases in muscular strength and neuroplasticity in people living with chronic incomplete spinal cord injury (SCI), but how it affects motor unit discharge rates is unknown. Motor unit spike times were identified from high-density surface electromyograms during maximal voluntary contractions and tracked from before to after AIH. Motor unit discharge rates were increased following AIH. These findings suggest that AIH can facilitate motoneuron function in people with incomplete SCI.

Effects of Robotic Postural Stand Training with Epidural Stimulation on Sitting Postural Control in Individuals with Spinal Cord Injury: A Pilot Study.

(1) Background. High-level spinal cord injury (SCI) disrupts trunk control, leading to an impaired performance of upright postural tasks in sitting and standing. We previously showed that a novel robotic postural stand training with spinal cord epidural stimulation targeted at facilitating standing (Stand-scES) largely improved standing trunk control in individuals with high-level motor complete SCI. Here, we aimed at assessing the effects of robotic postural stand training with Stand-scES on sitting postural control in the same population. (2) Methods. Individuals with cervical (n = 5) or high-thoracic (n = 1) motor complete SCI underwent approximately 80 sessions (1 h/day; 5 days/week) of robotic postural stand training with Stand-scES, which was performed with free hands (i.e., without using handlebars) and included periods of standing with steady trunk control, self-initiated trunk and arm movements, and trunk perturbations. Sitting postural control was assessed on a standard therapy mat, with and without scES targeted at facilitating sitting (Sit-scES), before and after robotic postural stand training. Independent sit time and trunk center of mass (CM) displacement were assessed during a 5 min time window to evaluate steady sitting control. Self-initiated antero-posterior and medial-lateral trunk movements were also attempted from a sitting position, with the goal of covering the largest distance in the respective cardinal directions. Finally, the four Neuromuscular Recovery Scale items focused on sitting trunk control (Sit, Sit-up, Trunk extension in sitting, Reverse sit-up) were assessed. (3) Results. In summary, neither statistically significant differences nor large Effect Size were promoted by robotic postural stand training for the sitting outcomes considered for analysis. (4) Conclusions. The findings of the present study, together with previous observations, may suggest that robotic postural stand training with Stand-scES promoted trunk motor learning that was posture- and/or task-specific and, by itself, was not sufficient to significantly impact sitting postural control.

High-intensity interval training with functional electrical stimulation cycling for incomplete spinal cord injury patients: A pilot feasibility study.

Consequences of spinal cord injury (SCI) with a sedentary lifestyle will progress to muscle weakness and muscle atrophy, leading to muscle fatigue. This study aimed to determine the feasibility and preliminary effects of high-intensity interval training (HIIT) using functional electrical stimulation (FES) cycling on changes in thigh muscle volume and muscle strength, in patients with incomplete SCI. Eight incomplete SCI patients (mean age 50 years; 6 women) with stable SCI paraplegia (mean 6.75 years since injury) participated in the HIIT FES cycling (85%-90% peak Watts; 4 × 4-min intervals) three times a week (over 6 weeks). The main outcomes were adherence, participant acceptability, and adverse events. Secondary outcomes were muscle strength (peak torque) and leg volume changes. Our findings revealed that the program was well-received by participants, with high levels of adherence, positive feedback, and satisfaction, suggesting that it could be a promising option for individuals seeking to enhance their lower body strength and muscle mass. Additionally, all participants successfully completed the training without any serious adverse events, indicating that the program is safe for use. Finally, we found that the 6-week HIIT FES leg cycling exercise program resulted in notable improvements in isometric peak torque of the quadriceps (range 13.9%-25.6%), hamstring muscle (18.2%-23.3%), and leg volume (1.7%-18.2%). This study highlights HIIT FES leg cycling exercise program potential as an effective intervention for improving lower limb muscle function.

Molecular mechanisms of spinal cord injury repair across vertebrates: A comparative review.

In humans and other adult mammals, axon regeneration is difficult in axotomized neurons. Therefore, spinal cord injury (SCI) is a devastating event that can lead to permanent loss of locomotor and sensory functions. Moreover, the molecular mechanisms of axon regeneration in vertebrates are not very well understood, and currently, no effective treatment is available for SCI. In striking contrast to adult mammals, many nonmammalian vertebrates such as reptiles, amphibians, bony fishes and lampreys can spontaneously resume locomotion even after complete SCI. In recent years, rapid progress in the development of next-generation sequencing technologies has offered valuable information on SCI. In this review, we aimed to provide a comparison of axon regeneration process across classical model organisms, focusing on crucial genes and signalling pathways that play significant roles in the regeneration of individually identifiable descending neurons after SCI. Considering the special evolutionary location and powerful regenerative ability of lamprey and zebrafish, they will be the key model organisms for ongoing studies on spinal cord regeneration. Detailed study of SCI in these model organisms will help in the elucidation of molecular mechanisms of neuron regeneration across species.

Effect of Intermittent Theta Burst Stimulation Dual-Target Stimulation on Lower Limb Function in Patients with Incomplete Spinal Cord Injury: A Randomized, Single-Blind, Sham-Controlled Study

To explore the influence of intermittent theta burst stimulation (iTBS) dual-target stimulation on lower limb function in patients with incomplete spinal cord injury (iSCI). A randomized, single -blind, sham-controlled trial was used in this study. Thirty iSCI patients with lower limb dysfunction meeting the inclusion criteria were randomly divided into a sham group and an iTBS group, with 15 cases in each group. The iTBS group received conventional rehabilitation therapy combined with iTBS dual-target stimulation on the central cerebral sulcus and the nerve root of the spinal cord injury segment. The sham group was treated with conventional rehabilitation therapy combined with iTBS dual-target sham stimulation therapy. Comprehensive functional assessment was performed on all patients before treatment, on the day 3 and day 21 of treatment. The main evaluation indicators were as follows: amplitude and latency of motor-evoked potential (MEP) in the anterior tibial muscles of both lower limbs, latency of sensory-evoked potential (SEP) of both lower limbs, knee flexor strength and knee extensor strength, lower extremity motor score (LEMS), lower extremity sensory score, spinal cord independence measure (SCIM) score, and gait parameters (stride speed, stride frequency, stride length, and ground reaction force). On day 21 of treatment, in the iTBS group, the MEP amplitude of the anterior tibial muscles increased, the latency of MEP shortened, knee flexor strength and knee extensor strength increased, and the LEMS and SCIM score of both lower limbs increased. In addition, there were statistically significant differences in the muscle strength of the knee flexion muscle, knee extensor muscle, MEP amplitude, LEMS, and SCIM between the 2 groups (P < 0.05). Among the 10 patients who could walk with an assisted walker, the step length and step frequency of the iTBS group were increased compared with the sham group after treatment (P < 0.01), and the ground reaction force was increased (P < 0.05). There was no significant difference in the lower extremity sensory score of the lower limbs between the 2 groups (P>0.05). ITBS dual-target stimulation can significantly improve the motor function of both lower limbs in patients with iSCI but does not significantly improve the sensory function of both lower limbs. Therefore, this treatment mode may participate in the reconstruction and repair of some nerve circuits in patients with iSCI. In addition, iTBS dual-target stimulation can improve the ability of iSCI patients to perform daily living.

Combining Neuromodulation Strategies in Spinal Cord Injury Gait Rehabilitation: A Proof of Concept, Randomized, Crossover Trial

ObjectivesTo evaluate if acute intermittent hypoxia (AIH) coupled with transcutaneous spinal cord stimulation (tSCS) enhances task-specific training and leads to superior and more sustained gait improvements as compared with each of these strategies used in isolation in persons with chronic, incomplete spinal cord injury. DesignProof of concept, randomized crossover trial. SettingOutpatient, rehabilitation hospital. InterventionsTen participants completed 3 intervention arms: (1) AIH, tSCS, and gait training (AIH + tSCS); (2) tSCS plus gait training (SHAM AIH + tSCS); and (3) gait training alone (SHAM + SHAM). Each arm consisted of 5 consecutive days of intervention with a minimum of a 4-week washout between arms. The order of arms was randomized. The study took place from December 3, 2020, to January 4, 2023. Main Outcome Measures10-meter walk test at self-selected velocity (SSV) and fast velocity, 6-minute walk test, timed Up and Go (TUG) and secondary outcome measures included isometric ankle plantarflexion and dorsiflexion torque ResultsTUG improvements were 3.44 seconds (95% CI: 1.24-5.65) significantly greater in the AIH + tSCS arm than the SHAM AIH + tSCS arm at post-intervention (POST), and 3.31 seconds (95% CI: 1.03-5.58) greater than the SHAM + SHAM arm at 1-week follow up (1WK). SSV was 0.08 m/s (95% CI: 0.02-0.14) significantly greater following the AIH + tSCS arm than the SHAM AIH + tSCS at POST. Although not significant, the AIH + tSCS arm also demonstrated the greatest average improvements compared with the other 2 arms at POST and 1WK for the 6-minute walk test, fast velocity, and ankle plantarflexion torque. ConclusionsThis pilot study is the first to demonstrate that combining these 3 neuromodulation strategies leads to superior improvements in the TUG and SSV for individuals with chronic incomplete spinal cord injury and warrants further investigation.

Descriptive Study of Earthquake-Related Spinal Cord Injury in Türkiye-Kahramanmaraş

Objective: We aimed to review the epidemiological data of patients who were rescued from under the rubble in the Kahramanmaraş earthquakes on February 6 and developed earthquake-related spinal vertebral fractures. Materials and Methods: Our study included 69 patients with spinal vertebral fractures and/or spinal cord injuries (SCIs) who were admitted to the Physical Medicine and Rehabilitation Clinic of Adana City Training and Research Hospital after the 6 February Kahramanmaraş Pazarcık and Elbistan earthquakes. Patients with peripheral nerve damage or loss of muscle strength due to pelvic and extremity fractures were not included in the study. Results: The mean age of the patients was 40.43±15.24 years (min=8-max=72). The median time of rescue from under the rubble was 15 (1-106) hours. The median visual analogue scale (VAS) pain score was 7 (0-10). 69.6% of the patients were female. Among the patients with a vertebral spinal injury, 72.5% had an incomplete SCI and 27.5% had a complete SCI. 84.5% of the patients underwent surgery, and posterior spinal instrumentation was performed in 56.5% of them. Conclusion: There has been a significant increase in the number of SCI cases after the Kahramanmaraş earthquakes. Rehabilitation centers should be established, patients' access to these centers should be facilitated, and complications should thus be prevented or optimized. Injured people should be helped to return to their social lives. Keywords: February 6th Kahramanmaraş, Earthquake, Spinal Cord Injury