Chronic Spinal Cord Injury Research Articles

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.

Regenerative medicine for spinal cord injury using induced pluripotent stem cells: from animals to humans

Abstract Spinal cord injury (SCI) results in permanent neurological dysfunction and neuropathic pain. To address this pathology, we recently conducted a clinical study in which we transplanted neural precursor cells (NPCs) derived from human induced pluripotent stem cells into patients during the subacute phase of SCI. One of the therapeutic mechanisms of cell transplantation is the formation of synaptic connections with the host's neural tissues, which we demonstrated using a chemogenetic tool. In addition, we have developed innovative strategies to enhance the effectiveness of cell transplantation through gene therapy. Moreover, our current study is focused on developing cell therapy for chronic SCI, a more challenging pathology characterized by the formation of cavities and scar tissue. In such situations, transplanting NPCs with neurogenic properties could effectively penetrate scar tissue and form functional synapses with the host neurons. To improve the outcomes of cell transplantation alone, we have found that incorporating rehabilitation is beneficial. In animal models of SCI, we have established an effective rehabilitative training program in which NPCs were transplanted during the chronic phase. Robotic rehabilitation has demonstrated improvements in gait ability and trunk function in clinical situations. Therefore, regenerative medicine shows promise for chronic SCI, particularly when rehabilitation strategies are incorporated.

Muscle-restricted knockout of connexin 43 and connexin 45 accelerates and improves locomotor recovery after contusion spinal cord injury

Traumatic spinal cord injury (SCI) results in the disruption of physiological systems below the level of the spinal lesion. Connexin hemichannels (CxHCs) are membrane-bound, non-selective pore proteins that are lost in mature myofibers but reappear de novo on the sarcolemma after peripheral denervation, chronic SCI, diabetes, and severe systemic stress such as sepsis. Cx43 and Cx45 have been implicated as the major CxHCs present in diseased muscle, and muscle-restricted knockout of these genes reduces muscle atrophy after denervation, likely by reducing excess calcium influx with resultant inflammasome activation. A muscle-restricted Cx43/45 conditional knockout (mKO) mouse model was developed and tested to check whether it would improve outcomes following either a complete spinal cord transection at the level of thoracic vertebrae-9 (T9) or a motor-incomplete T9 impact-contusion SCI. mKO had no effect on the body mass after complete T9 transection. There was reduced atrophy of the plantaris 15 days post-SCI that was not associated with molecular markers of inflammation, hypertrophic/atrophic protein signaling, or protein and mRNA expression related to mitochondrial integrity and function. mKO mice had faster and greater locomotor recovery across 28 days after a motor-incomplete contusion SCI with no differences in spared white matter; male mKO mice generally had greater muscle mass than genotype controls post-injury, but muscle sparing was not observed in female mKO mice post-injury. The data establish a new paradigm where muscle Cx43/45 may contribute to the tissue crosstalk that determines the neuromuscular function of sub-lesional musculature after motor-incomplete SCI in a sex-dependent manner. Our novel findings should promote investigation to develop innovative treatment strategies to improve the function and quality of life for persons with SCI.

Automatic Assist Level Adjustment Function of a Gait Exercise Rehabilitation Robot with Functional Electrical Stimulation for Spinal Cord Injury: Insights from Clinical Trials.

This study aimed to identify whether the combined use of functional electrical stimulation (FES) reduces the motor torque of a gait exercise rehabilitation robot in spinal cord injury (SCI) and to verify the effectiveness of the developed automatic assist level adjustment in people with paraplegia. Acute and chronic SCI patients (1 case each) performed 10 min of gait exercises with and without FES using a rehabilitation robot. Reinforcement learning was used to adjust the assist level automatically. The maximum torque values and assist levels for each of the ten walking cycles when walking became steady were averaged and compared with and without FES. The motor's output torque and the assist level were measured as outcomes. The assist level adjustment allowed both the motor torque and assist level to decrease gradually to a steady state. The motor torque and the assist levels were significantly lower with the FES than without the FES under steady conditions in both cases. No adverse events were reported. The combined use of FES attenuated the motor torque of a gait exercise rehabilitation robot for SCI. Automatic assistive level adjustment is also useful for spinal cord injuries.

Validation of the Patient Activation Measure (PAM-13) among individuals with chronic spinal cord injury in mainland China

Context/objective: The 13-item Patient Activation Measure (PAM-13) is the most widely used generic patient activation measure, but spinal cord injury (SCI) related psychometric evaluation of PAM-13 has not been explored globally. This study aimed to assess the validity of the Chinese version of the PAM-13 (PAM-13-C) for individuals with chronic spinal cord injury (CSCI). Design: Cross-sectional study. Setting: Shanghai Sunshine Rehabilitation Center, and some participants were recruited in a WeChat group (the most commonly used social media platform in China). Participants: 284 individuals with spinal cord injury who had lived with the injury for ≥0.5 year. Interventions: NA. Outcome measures: The PAM-13-C, global QoL, seven-item generalized anxiety disorder scale (GAD-7) and nine-item patient health questionnaire (PHQ-9), and General Self-Efficacy Scale (GSES) were used. Results: The mean (SD) PAM-13-C score was 57.4 (16.5). The highest percentage of NA could be observed in item 9 (12.0%). Floor and ceiling effects of the total scores of PAM-13-C were small (0.7% and 6.7%), but a ceiling effect could be observed among all items. Exploratory Factor Analysis supported a one-factor model of the PAM-13-C (CFI = 0.97; RMSEA = 0.07). Construct validity was established through correlation analysis among the PAM-13-C, GAD-7/PHQ-9, global QoL, and GSES. The PAM-13-C demonstrated excellent internal consistency (Cronbach’s α = 0.95) and acceptable test-retest reliability. Conclusion: The PAM-13-C is a reliable and valid measure of patient activation for individuals with CSCI in China.

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.

Intravenous Infusion of Autologous Mesenchymal Stem Cells Expanded in Auto Serum for Chronic Spinal Cord Injury Patients: A Case Series

Objective: The safety, feasibility, and potential functional improvement following the intravenous infusion of mesenchymal stem cells (MSCs) were investigated in patients with chronic severe spinal cord injury (SCI). Methods: The intravenous infusion of autologous MSCs cultured in auto-serum under Good Manufacturing Practices (GMP) was administered to seven patients with chronic SCI (ranging from 1.3 years to 27 years after the onset of SCI). In addition to evaluating feasibility and safety, neurological function was evaluated using the American Spinal Injury Association Impairment Scale (AIS), International Standards for Neurological Classification of Spinal Cord Injury (ISCSCI-92), and Spinal Cord Independence Measure III (SCIM-III). Results: No serious adverse events occurred. Neither CNS tumors, abnormal cell growth, nor neurological deterioration occurred in any patients. While this initial case series was not blinded, significant functional improvements and increased quality of life (QOL) were observed at 90 and 180 days post-MSC infusion compared to pre-infusion status. One patient who had an AIS grade C improved to grade D within six months after MSC infusion. Conclusions: This case series suggests that the intravenous infusion of autologous MSCs is a safe and feasible therapeutic approach for chronic SCI patients. Furthermore, our data showed significant functional improvements and better QOL after MSC infusion in patients with chronic SCI. A blind large-scale study will be necessary to fully evaluate this possibility.

Discriminating fingerprints of chronic neuropathic pain following spinal cord injury using artificial neural networks and mass spectrometry analysis of female mice serum

Spinal cord injury (SCI) often leads to central neuropathic pain, a condition associated with significant morbidity and is challenging in terms of the clinical management. Despite extensive efforts, identifying effective biomarkers for neuropathic pain remains elusive. Here we propose a novel approach combining matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with artificial neural networks (ANNs) to discriminate between mass spectral profiles associated with chronic neuropathic pain induced by SCI in female mice. Functional evaluations revealed persistent chronic neuropathic pain following mild SCI as well as minor locomotor disruptions, confirming the value of collecting serum samples. Mass spectra analysis revealed distinct profiles between chronic SCI and sham controls. On applying ANNs, 100% success was achieved in distinguishing between the two groups through the intensities of m/z peaks. Additionally, the ANNs also successfully discriminated between chronic and acute SCI phases. When reflexive pain response data was integrated with mass spectra, there was no improvement in the classification. These findings offer insights into neuropathic pain pathophysiology and underscore the potential of MALDI-TOF MS coupled with ANNs as a diagnostic tool for chronic neuropathic pain, potentially guiding attempts to discover biomarkers and develop treatments.

ID: 332552 Mapping Hybrid Structural-Functional Connectome in Individuals with Chronic Spinal Cord Injury and Neuropathic Pain

ID: 332552 Mapping Hybrid Structural-Functional Connectome in Individuals with Chronic Spinal Cord Injury and Neuropathic Pain

Predictive value of dynamic diffusion tensor imaging for surgical outcomes in patients with cervical spondylotic myelopathy

BackgroundCervical spondylotic myelopathy (CSM) is the most common chronic spinal cord injury with poor surgical and neurologic recovery in the advanced stages of the disease. DTI parameters can serve as important biomarkers for CSM prognosis. The study aimed to investigate the predictive value of dynamic diffusion tensor imaging (DTI) for the postoperative outcomes of CSM.MethodsOne hundred and five patients with CSM who underwent surgery were included in this study. Patients were assessed using the Modified Japanese Orthopedic Association Score (mJOA) before and one year after surgery and then divided into groups with good (≥ 50%) and poor (< 50%) prognoses according to the rate of recovery. All patients underwent preoperative dynamic magnetic resonance imaging of the cervical spine, including T2WI and DTI in natural(N), extension (E), and flexion (F) positions. ROM, Cross-sectional area, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were measured at the narrowest level in three neck positions. Univariate and multivariate logistic regression were used to identify risk factors for poor postoperative recovery based on clinical characteristics, dynamic T2WI, and DTI parameters. Predictive models were developed for three different neck positions.ResultsForty-four (41.9%) patients had a good postoperative prognosis, and 61 (58.1%) had a poor prognosis. Univariate analysis showed statistically significant differences in diabetes, number of compression segments, preoperative mJOA score, cross-sectional area ((Area-N), (Area-E), (Area-F)), ADC((ADC-N), (ADC-E), (ADC-F)) and FA (((FA-N), (FA-E), (FA-F)) (p < 0.05). Multivariable logistic regression showed that natural neck position: Area-N ([OR] 0.226; [CI] 0.069–0.732, p = 0.013),FA-N([OR]3.028;[CI]1.12–8.19,p = 0.029); extension ne-ck position: Area-E([OR]0.248;[CI]0.076–0.814,p = 0.021), FA-E([OR]4.793;[CI]1.737–13.228,p = 0.002);And flextion neck postion: Area-F([OR] 0.288; [CI] 0.095–0.87, p = 0.027),FA-F ([OR] 2.964; [CI] 1.126–7.801, p = 0.028) were independent risk factors for poor prognosis.The area under the curve (AUC) of the prediction models in the natural neck position, extension neck position, and flexion neck positions models were 0.708[(95% CI:0.608∼0.808), P < 0.001]; 0.738 [(95% CI:0.641∼0.835), P < 0.001]; 0.703 [(95% CI:0.602∼0.803), P < 0.001], respectively.ConclusionDynamic DTI can predict postoperative outcomes in CSM. Reduced FA in the extension position is a valid predictor of poor postoperative neurological recovery in patients with CSM.

The effect of home-based neuromuscular electrical stimulation-resistance training and protein supplementation on lean mass in persons with spinal cord injury: A pilot study.

In persons with a spinal cord injury (SCI), resistance training using neuromuscular electrical stimulation (NMES-RT) increases lean mass in the lower limbs. However, whether protein supplementation in conjunction with NMES-RT further enhances this training effect is unknown. In this randomized controlled pilot trial, 15 individuals with chronic SCI engaged in 3 times/week NMES-RT, with (NMES+PRO, n = 8) or without protein supplementation (NMES, n = 7), for 12 weeks. Before and after the intervention, whole body and regional body composition (DXA) and fasting glucose and insulin concentrations were assessed in plasma. Adherence to the intervention components was ≥96%. Thigh lean mass was increased to a greater extent after NMES+PRO compared to NMES (0.3 (0.2, 0.4) kg; p < 0.001). Furthermore, fasting insulin concentration and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were decreased similarly in both groups (fasting insulin: 1 [-9, 11] pmol∙L-1; HOMA-IR: 0.1 [-0.3, 0.5] AU; both p ≥ 0.617). Twelve weeks of home-based NMES-RT increased thigh lean mass, an effect that was potentiated by protein supplementation. In combination with the excellent adherence and apparent improvement in cardiometabolic health outcomes, these findings support further investigation through a full-scale randomized controlled trial.

A Kinematic Deviation Index (KDI) for Evaluation of Forelimb Function in Rodents.

Rodent models are widely used to study neurological conditions and assess forelimb movement to measure function performance, deficit, recovery and treatment effectiveness. Traditional assessment methods based on endpoints such as whether the task is accomplished, while easy to implement, provide limited information on movement patterns important to assess different functional strategies. On the other side, detailed kinematic analysis provides granular information on the movement patterns but is difficult to compare across laboratories, and may not translate to clinical metrics of upper limb function. To address these limitations, we developed and validated a kinematic deviation index (KDI) for rodents that mimics current trends in clinical research. The KDI is a unitless summary score that quantifies the difference between an animal movement during a task and its optimal performance derived from spatiotemporal marker sequences without pre-specifying movements. We demonstrate the utility of KDI in assessing reaching and grasping in mice and validate its discrimination between trial endpoints in healthy animals. Furthermore, we show KDI sensitivity to interventions, including acute and chronic spinal cord injury and optogenetic disruption of sensorimotor circuits. The KDI provides a comprehensive measure of motor function that bridges the gap between detailed kinematic analysis and simple success/failure metrics, offering a valuable tool for assessing recovery and compensation in rodent models of neurological disorders.

Development of a chronic compression spinal cord injury model in neonatal and adult rats.

Spinal cord injury presents a significant burden globally, with traumatic spinal cord injury being the predominant cause historically. However, nontraumatic spinal cord injury (NTSCI) is emerging as a significant contributor, particularly in developed nations, yet it remains poorly understood due to underreporting and misclassification. NTSCI, spanning various etiologies such as bony growths, vascular conditions, infections, neoplastic conditions, and immune disorders, poses unique challenges in diagnosis and treatment, often resulting in lifelong morbidity. This study addresses the lack of suitable animal models for NTSCI research, especially in neonatal animals. Utilizing a solid spacer approach, we developed a compression NTSCI model applicable to both neonatal and adult Sprague-Dawley rats. Through anatomical measurements and invivo experiments, we confirmed the feasibility and safety of the spacer insertion procedure and observed no acute off-target effects. The versatility of this model lies in its adaptability to different ages of rats, offering a cost-effective and reproducible means to induce graded injuries. Moreover, behavioral assessments demonstrated observable hindlimb function, validating the model's utility for studying functional outcomes. Although challenges persist, particularly in accounting for spinal column growth in neonatal animals, this model fills a crucial gap in pediatric NTSCI research. By providing a platform to investigate pathophysiological mechanisms and test potential treatments, it offers promising avenues for advancing our understanding and management of pediatric NTSCI.

Self-reported benzodiazepine use among adults with chronic spinal cord injury in the southeastern USA: associations with demographic, injury, and opioid use characteristics.

Cross-sectional cohort study. To examine: (1) the self-reported frequency of specific prescription benzodiazepine use, (2) concurrent benzodiazepine and opioid use, and (3) sociodemographic, SCI, and opioid use factors associated with frequent benzodiazepine use. Community. Participants included 918 community dwelling adults with chronic ( > 1 year) traumatic SCI originally identified from a specialty hospital or a state-based surveillance system. Self-reported frequency of specific prescription benzodiazepines and opioids used, concurrent use, and factors associated with use were assessed. Twenty percent reported any benzodiazepine use in the past year and 13% reported at least weekly use. Concurrent daily or weekly use of benzodiazepines and opioids was reported by 6.5%, with those individuals taking an average of 1.1 (0.4) benzodiazepines and 1.4 (0.6) opioids. Compared to younger adults, those 50-65 years old had lower odds of at least weekly benzodiazepine use (OR = 0.50, 95% CI, 0.29-0.89, p-value = 0.02). Non-Hispanic Blacks reported lower use of benzodiazepines compared to non-Hispanic whites (OR = 0.32, 95% CI, 0.15-0.68, p-value = <0.01). Weekly opioid use was associated with higher odds of using benzodiazepines (OR = 3.10, 95%CI, 1.95-4.95, p-value = <0.01). Benzodiazepine use was commonly reported among those with SCI. Despite the potential risks, a high portion of those who reported benzodiazepine use also reported prescription opioid use. The findings highlight the need for monitoring of prescription medication use to avoid potentially risky concurrent use and adverse outcomes.

Anxiety and Depression after Spinal Cord Injury: A Cross-Sectional Study.

Spinal cord injury (SCI) is a life-changing event that often results in chronic physical damage and challenges in maintaining a good quality of life as it affects every aspect of life. These situations require adjustment, increasing vulnerability to psychological disorders. The objective of this study was to evaluate the impact of SCI on psychological morbidity in individuals with subacute and chronic SCI. The present investigation was designed to determine the presence and extent of psychological complications following SCI. We used two reliable questionnaires and validated psychological assessments to study depression (BDI) and anxiety (STAI), a broad range of factors derived from SCI that may be predictors of certain psychological problems. The psychological assessment revealed alterations in depression and anxiety, although the data do not exceed those of previous investigations. No clear predisposing factors leading to certain psychological pathologies were found. In addition, individuals in the subacute and chronic stages differed in their scores. In individuals with SCI, identifying predictors of psychological problems is difficult, but premature assessment of mental state is essential. This early diagnosis of possible problems or changes at the mental level is fundamental and necessary to avoid possible alterations at the cognitive level and, of course, more serious mental complications.

Pharmacological management of secondary chronic spinal cord injury: a systematic review.

Spinal cord injury (SCI) may bring lifelong consequences for affected patients and a high financial burden to the health care system. Published peer-reviewed scientific articles identified from EMBASE, Google Scholar, PubMed and Scopus. Surgery and blood pressure management are the main targets in acute SCI to avoid secondary damage. The management of secondary chronic SCI is challenging, with unpredictable outcomes. Given the lack of consensus on pharmacological therapy for acute and secondary chronic SCI, the present study analyses the currently available drugs and treatment options to manage secondary chronic SCI. Different approaches exist for the pharmacological management of secondary chronic SCI. One of the most investigated drugs, 4-aminopyridine, improves central motor conduction and shows improvement in neurological signs. Positive results in different areas have been observed in patients receiving the anti-spastic drugs tizanidine and baclofen or Granulocyte colony-stimulating factor. Growth hormone showed only minimal or no significant effects, and the therapy of secondary chronic SCI with riluzole has been poorly researched to date.

Exoskeletal-assisted walking combined with transcutaneous spinal cord stimulation to improve bone health in persons with spinal cord injury: study protocol for a prospective randomised controlled trial

IntroductionPersons with non-ambulatory spinal cord injury (SCI) undergo immediate unloading of the skeleton and, as a result, have marked loss of bone mineral density below the level of lesion that...

Effects of exercise on autonomic cardiovascular control in individuals with chronic, motor-complete spinal cord injury: an exploratory randomised clinical trial.

Secondary analysis of a clinical trial. To assess the impact of 6 months of armcycle ergometry training (ACET), or body weight-supported treadmill training (BWSTT), on autonomic cardiovascular responses to a laboratory sit-up test (SUT) in individuals with chronic (≥1-year post-injury) spinal cord injury (SCI). Tertiary Rehabilitation Centre, Vancouver, Canada. Sixteen individuals with motor-complete (American Spinal Injury Association Impairment Scale A-B) SCI between the fourth cervical and sixth thoracic spinal cord segments, aged 39 ± 11 years, were assessed. Participants were randomized to receive 72 sessions of moderate-to-vigorous intensity ACET (n = 8) or passive BWSTT (n = 8). Changes in mean arterial pressure (finger plethysmography), hemodynamics (Modelflow® method), and heart rate/heart rate variability (HR/HRV; electrocardiography) were measured in response toa SUT before and after 6 months of exercise training. Spontaneous cardiovagal baroreflex sensitivity (cvBRS) was assessed using the sequence method. Neither ACET nor BWSTT impacted hemodynamic responses to SUT or the incidence of orthostatic hypotension (all P > 0.36). ACET increased HR (P < 0.01, ηp2 = 0.34) and high frequency (HF) power HRV responses (P < 0.01, ηp2 = 0.42) to SUT following 6 months of training while BWSTT did not. Consistent with this, cvBRS improved (P < 0.05, ηp2 = 0.16) only following ACET. Improvements in cvBRS were correlated with both the HR (r = 0.726, P < 0.0001) and HF power (r = -0.484, P < 0.01) responses to SUT. Six months of ACET, but not BWSTT, improved cardiovagal baroreflex control of HR but had no effect on BP responses to SUT in individuals with chronic, motor-complete SCI. Canadian Institutes of Health Research (CIHR) CLINICAL TRIAL REGISTRATION: NCT01718977.

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.

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.