Chronic Motor Complete Spinal Cord Research Articles

A case study of percutaneous epidural stimulation to enable motor control in two men after spinal cord injury

Two persons with chronic motor complete spinal cord injury (SCI) were implanted with percutaneous spinal cord epidural stimulation (SCES) leads to enable motor control below the injury level (NCT04782947). Through a period of temporary followed by permanent SCES implantation, spinal mapping was conducted primarily to optimize configurations enabling volitional control of movement and training of standing and stepping as a secondary outcome. In both participants, SCES enabled voluntary increased muscle activation and movement below the injury and decreased assistance during exoskeleton-assisted walking. After permanent implantation, both participants voluntarily modulated induced torques but not always in the intended directions. In one participant, percutaneous SCES enabled motor control below the injury one-day following temporary implantation as confirmed by electromyography. The same participant achieved independent standing with minimal upper extremity self-balance assistance, independent stepping in parallel bars and overground ambulation with a walker. SCES via percutaneous leads holds promise for enhancing rehabilitation and enabling motor functions for people with SCI.

Transspinal stimulation and step training alter function of spinal networks in complete spinal cord injury.

Pilot study (case series). The objective of this study was to establish spinal neurophysiological changes following high-frequency transspinal stimulation during robot-assisted step training in individuals with chronic motor complete spinal cord injury (SCI). University research laboratory (Klab4Recovery). Four individuals with motor complete SCI received an average of 18 sessions of transspinal stimulation over the thoracolumbar region with a pulse train at 333 Hz during robotic-assisted step training. Each session lasted ~1 h, with an average of 240 stimulations delivered during each training session. Before and after the combined intervention, we evaluated the amplitude modulation of the long-latency tibialis anterior (TA) flexion reflex and transspinal evoked potentials (TEP) recorded from flexors and extensors during assisted stepping, and the TEP recruitment curves at rest. The long-latency TA flexion reflex was depressed in all phases of the step cycle and the phase-dependent amplitude modulation of TEPs was altered during assisted stepping, while spinal motor output based on TEP recruitment curves was increased after the combined intervention. This is the first study documenting noninvasive transspinal stimulation coupled with locomotor training depresses flexion reflex excitability and concomitantly increases motoneuron output over multiple spinal segments for both flexors and extensors in people with motor complete SCI. While both transspinal stimulation and locomotor training may act via similar activity-dependent neuroplasticity mechanisms, combined interventions for rehabilitation of neurological disorders has not been systematically assessed. Our current findings support locomotor training induced neuroplasticity may be augmented with transspinal stimulation.

Exoskeletal-assisted walking may improve seated balance in persons with chronic spinal cord injury: a pilot study.

Pre-post intervention. To explore the potential effect of exoskeletal-assisted walking (EAW) on seated balance for persons with chronic motor complete spinal cord injury (SCI). A SCI research center. Eight participants who were over 18 years of age with chronic SCI and used a wheelchair for mobility were enrolled. Seven able-bodied participants were used for normal seated balance comparative values. Participants with chronic SCI received supervised EAW training using a powered exoskeleton (ReWalkTM) for a median 30 sessions (range from 7 to 90 sessions). Before and after EAW training, seated balance testing outcomes were collected using computerized dynamic posturography, providing measurements of endpoint excursion (EPE), maximal excursion (MXE), and directional control (DCL). Modified functional reach test (MFRT) and the sub-scales of physical functioning and role limitations due to physical health from the Short Form (36) Health Survey (SF-36) were used to identify changes in functional activities. After EAW training, seated balance significantly improved in total-direction EPE and MXE (P < 0.01 and P < 0.017 respectively). The results of MFRT and sub-scales of physical functioning and role limitations due to physical health improved after EAW training but were not statistically significant. EAW training may have the potential to improve seated balance for persons with chronic motor complete SCI. Due to the limitations of the study, such as small sample size and lack of a control group, further studies are needed to clarify the effect of improving seated balance through EAW training.

Spinal motor mapping by epidural stimulation of lumbosacral posterior roots in humans.

SummaryEpidural electrical stimulation of the spinal cord is an emergent strategy for the neurological recovery of lower-extremity motor function. Motoneuron pools are thought to be recruited by stimulation of posterior roots. Here, we linked electromyographic data of epidurally evoked lower-extremity responses of 34 individuals with upper motoneuron disorders to a population model of the spinal cord constructed using anatomical parameters of thousands of individuals. We identified a relationship between segmental stimulation sites and activated spinal cord segments, which made spinal motor mapping from epidural space possible despite the complex anatomical interface imposed by the posterior roots. Our statistical approach provided evidence for low-threshold sites of posterior roots and effects of monopolar and bipolar stimulation previously predicted by computer modeling and allowed us to test the impact of different upper motoneuron disorders on the evoked responses. Finally, we revealed a statistical association between intraoperative and postoperative mapping of the spinal cord.

Epidural stimulation for cardiovascular function increases lower limb lean mass in individuals with chronic motor complete spinal cord injury.

What is the central question of this study? Spinal cord injury results in paralysis and deleterious neuromuscular and autonomic adaptations. Lumbosacral epidural stimulation can modulate motor and/or autonomic functions. Does long-term epidural stimulation for normalizing cardiovascular function affect leg muscle properties? What is the main finding and its importance? Leg lean mass increased after long-term epidural stimulation for cardiovascular function, which was applied in the sitting position and did not activate the leg muscles. Leg muscle strength and fatigue resistance, assessed in a subgroup of individuals, also increased. These adaptations might support interventions for motor recovery and warrant further mechanistic investigation. Chronic motor complete spinal cord injury (SCI) results in paralysis and deleterious neuromuscular and autonomic adaptations. Paralysed muscles demonstrate atrophy, loss of force and increased fatigability. Also, SCI-induced autonomic impairment results in persistently low resting blood pressure and heart rate, among other features. We previously reported that spinal cord epidural stimulation (scES) optimized for cardiovascular (CV) function (CV-scES), which is applied in sitting position and does not activate the leg muscles, can maintain systolic blood pressure within a normotensive range during quiet sitting and during orthostatic stress. In the present study, dual-energy X-ray absorptiometry collected from six individuals with chronic clinically motor complete SCI demonstrated that 88±11 sessions of CV-scES (7daysweek-1 ; 2hday-1 in four individuals and 5hday-1 in two individuals) over a period of ∼6months significantly increased lower limb lean mass (by 0.67±0.39kg or 9.4±8.1%; P<0.001). Additionally, muscle strength and fatigability data elicited by neuromuscular electrical stimulation in three of these individuals demonstrated a general increase (57±117%) in maximal torque output (between 2 and 44Nm in 14 of the 17 muscle groups tested overall) and torque-time integral during intermittent, fatiguing contractions (63±71%; between 7 and 230% in 16 of the 17 muscle groups tested overall). In contrast, whole-body mass and composition did not change significantly. In conclusion, long-term use of CV-scES can have a significant impact on lower limb muscle properties after chronic motor complete SCI.

Osteoporosis in the lower extremities in chronic spinal cord injury.

Cross-sectional study. To investigate the effect of chronic motor complete spinal cord injury (SCI) and sex on bone densitometry parameters of the hip, femoral neck, tibial epiphysis, and diaphysis and on long bone fractures. SCI rehabilitation center. Women and men with long-term (≥7 years) motor complete SCI were compared with able-bodied women and men. Dual-energy X-ray absorptiometry was used to assess bone densitometry parameters at the hip and femoral neck, whereas peripheral quantitative computed tomography was used for the tibial epiphysis and diaphysis. The data of 18 women and 25 men with SCI with a mean age of 54.7 ± 12.4 and 53.5 ± 8.6 years, respectively, were analyzed. As reference groups, 74 able-bodied women and 46 men with a mean age of 51.0 ± 13.1 and 50.9 ± 11.2 years were evaluated. Most bone densitometry values were significantly (p ≤ 0.033) lower in the SCI compared with the reference groups, including total bone mineral density at the distal tibial epiphysis (-58.0% in SCI women and -53.6% in SCI men). Fracture rates per 100 patient-years were 3.17 and 2.66 in women and men with SCI compared with 0.85 and 0.21 in able-bodied women and men, respectively. Compared with able-bodied women and men, individuals with chronic motor complete SCI showed considerably lower bone densitometry values and a higher historical fracture rate. These findings support the need for preventative and therapeutic strategies against bone loss in individuals with SCI.

Neurophysiological markers predicting recovery of standing in humans with chronic motor complete spinal cord injury

The appropriate selection of individual-specific spinal cord epidural stimulation (scES) parameters is crucial to re-enable independent standing with self-assistance for balance in individuals with chronic, motor complete spinal cord injury, which is a key achievement toward the recovery of functional mobility. To date, there are no available algorithms that contribute to the selection of scES parameters for facilitating standing in this population. Here, we introduce a novel framework for EMG data processing that implements spectral analysis by continuous wavelet transform and machine learning methods for characterizing epidural stimulation-promoted EMG activity resulting in independent standing. Analysis of standing data collected from eleven motor complete research participants revealed that independent standing was promoted by EMG activity characterized by lower median frequency, lower variability of median frequency, lower variability of activation pattern, lower variability of instantaneous maximum power, and higher total power. Additionally, the high classification accuracy of assisted and independent standing allowed the development of a prediction algorithm that can provide feedback on the effectiveness of muscle-specific activation for standing promoted by the tested scES parameters. This framework can support researchers and clinicians during the process of selection of epidural stimulation parameters for standing motor rehabilitation.

Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury

SummaryPersons with motor complete spinal cord injury, signifying no voluntary movement or sphincter function below the level of injury but including retention of some sensation, do not recover independent walking. We tested intense locomotor treadmill training with weight support and simultaneous spinal cord epidural stimulation in four patients 2.5 to 3.3 years after traumatic spinal injury and after failure to improve with locomotor training alone. Two patients, one with damage to the mid-cervical region and one with damage to the high-thoracic region, achieved over-ground walking (not on a treadmill) after 278 sessions of epidural stimulation and gait training over a period of 85 weeks and 81 sessions over a period of 15 weeks, respectively, and all four achieved independent standing and trunk stability. One patient had a hip fracture during training. (Funded by the Leona M. and Harry B. Helmsley Charitable Trust and others; ClinicalTrials.gov number, NCT02339233.)

Mechanomyography responses characterize altered muscle function during electrical stimulation-evoked cycling in individuals with spinal cord injury

BackgroundInvestigation of muscle fatigue during functional electrical stimulation (FES)-evoked exercise in individuals with spinal cord injury using dynamometry has limited capability to characterize the fatigue state of individual muscles. Mechanomyography has the potential to represent the state of muscle function at the muscle level. This study sought to investigate surface mechanomyographic responses evoked from quadriceps muscles during FES-cycling, and to quantify its changes between pre- and post-fatiguing conditions in individuals with spinal cord injury. MethodsSix individuals with chronic motor-complete spinal cord injury performed 30-min of sustained FES-leg cycling exercise on two days to induce muscle fatigue. Each participant performed maximum FES-evoked isometric knee extensions before and after the 30-min cycling to determine pre- and post- extension peak torque concomitant with mechanomyography changes. FindingsSimilar to extension peak torque, normalized root mean squared (RMS) and mean power frequency (MPF) of the mechanomyography signal significantly differed in muscle activities between pre- and post-FES-cycling for each quadriceps muscle (extension peak torque up to 69%; RMS up to 80%, and MPF up to 19%). Mechanomyographic-RMS showed significant reduction during cycling with acceptable between-days consistency (intra-class correlation coefficients, ICC = 0.51–0.91). The normalized MPF showed a weak association with FES-cycling duration (ICC = 0.08–0.23). During FES-cycling, the mechanomyographic-RMS revealed greater fatigue rate for rectus femoris and greater fatigue resistance for vastus medialis in spinal cord injured individuals. InterpretationMechanomyographic-RMS may be a useful tool for examining real time muscle function of specific muscles during FES-evoked cycling in individuals with spinal cord injury.

Sex dimorphism in the distribution of adipose tissue and its influence on proinflammatory adipokines and cardiometabolic profiles in motor complete spinal cord injury

Objective: We aimed to examine the influence of sex on the distribution of adipose tissue, as well as proinflammatory adipokine and cardiometabolic profiles, in chronic motor complete spinal cord injury (SCI).Design: Cross-sectional and correlational study.Setting: Academic rehabilitation hospital.Participants: Forty-seven individuals with chronic motor complete SCI classified according to sex (males: age 44.0 ± 10.9 y, body mass index (BMI) 27.2 ± 5.8, level of injury (LOI) C4 - L1; females: 42.0 ± 13.5 y, BMI 27.8 ± 6.6, LOI C4 - T11).Intervention: Not applicable.Outcome Measures: Visceral (VAT), subcutaneous (SAT), and total trunk (TTAT) adipose tissue volumes were assessed utilizing magnetic resonance imaging and a VAT:SAT ratio was calculated. Proinflammatory adipokines (tumor neurosis factor-α, interleukin-6, plasminogen activator inhibitor-1, thrombin-activatable fibrinolysis inhibitor, and high sensitivity c-reactive protein) and cardiovascular, carbohydrate, and lipid profiles were evaluated according to standard techniques.Results: VAT and VAT:SAT ratio were significantly greater in male participates with SCI (P ≤ 0.002), while SAT volume was significantly greater in female participants with SCI (P = 0.001). No difference was noted in TTAT between groups (P = 0.341). Male participants with SCI demonstrated lower high-density lipoprotein-cholesterol (HDLC) profiles and an elevated total cholesterol to HDLC ratio (P ≤ 0.003) compared with females. No other significant differences were found between groups concerning cardiometabolic profiles or proinflammatory adipokines; however, males exhibited poorer profiles overall. Proinflammatory adipokines significantly correlated with adipose tissue depots by sex (P < 0.05).Conclusion: The results show that sex influences the distribution of adipose tissue, and may influence proinflammatory and cardiometabolic profiles following SCI. The findings of this study highlight the need for further research with dietary modification and exercise to decrease health risks.

Abundance in proteins expressed after functional electrical stimulation cycling or arm cycling ergometry training in persons with chronic spinal cord injury

Study design: Longitudinal design.Objectives: The study determined the effects of two forms of exercise training on the abundance of two proteins, (glucose transporter-4 [GLUT-4], adenosine monophosphate kinase [AMPK]) involved in glucose utilization and the transcriptional coactivator that regulates the genes involved in energy metabolism and mitochondrial biogenesis (peroxisome proliferator-activated receptor (PPAR) coactivator 1 alpha [PGC-1α]), in muscles in men with chronic motor-complete spinal cord injury (SCI).Settings: Clinical trial at a Medical Center.Methods: Nine men with chronic motor-complete SCI participated in functional electrical stimulation lower extremity cycling (FES-LEC; n = 4) or arm cycling ergometer (arm-cycling ergometer [ACE]; n = 5) 5 days/week for 16 weeks. Whole body composition was measured by dual energy X-ray absorptiometry. An intravenous glucose tolerance test was performed to measure glucose effectiveness (Sg) and insulin sensitivity (Si). Muscle biopsies of the right vastus lateralis (VL) and triceps muscles were collected one week prior to and post the exercise training intervention.Results: Neither training intervention altered body composition or carbohydrate metabolism. GLUT-4 increased by 3.8 fold in the VL after FES training and increased 0.6 fold in the triceps after ACE training. PGC-1α increased by 2.3 fold in the VL after FES training and 3.8 fold in the triceps after ACE training. AMPK increased by 3.4 fold in the VL after FES training and in the triceps after ACE training.Conclusion: FES-LEC and ACE training were associated with greater protein expressions in the trained muscles by effectively influencing the abundance of GLUT-4, AMPK and PGC-1α. Thus, FES-LEC training of paralyzed muscle can modulate protein expression similar to that of trained and innervated muscle.

Severe spasticity in lower extremities is associated with reduced adiposity and lower fasting plasma glucose level in persons with spinal cord injury.

Cross-sectional study. To investigate the effects of severe lower extremity spasticity on anthropometric dimensions, body composition and metabolic profiles in persons with chronic motor complete spinal cord injury (SCI). Outpatient clinic. Fifty-five of the 61 participants were divided into two groups (no or mild spasticity group, 28; severe spasticity group, 27) based on the assessment of the extensor muscle spasticity according to the modified Ashworth scale. Anthropometric dimensions (waist circumference (WC), waist-to-height ratio (WtHR)), body composition (fat mass (FM), body fat percentage (BFP), fat-free mass (FFM), fat-free mass percentage (FFMP), bone mineral density (BMD)) and metabolic profiles (leptin, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c)) were compared between the two groups with different degree of spasticity. Spasticity of the extensor muscle group negatively correlated with BFP (r=-0.458, P<0.001). Patients with severe spasticity showed a lower WC and WtHR than those in the no or mild spasticity group (P=0.038, P=0.006, respectively). The FM, BFP, leptin and FPG of the severe spasticity group were significantly lower than those of the patients in the no or mild spasticity group (P=0.003, P<0.001, P<0.001 and P=0.037, respectively). However, no differences in BMD, total cholesterol, LDL, HDL, TG and HbA1c were observed between the groups. The results of this study suggest that severe spasticity in lower extremities is associated with reduced adiposity and lower FPG levels in persons with chronic motor complete SCI.

Muscle activity, cross-sectional area, and density following passive standing and whole body vibration: A case series

ObjectiveTo investigate the effects of intermittent passive standing (PS) and whole body vibration (WBV) on the electromyography (EMG) activity, cross-sectional area, and density of lower extremity muscles in individuals with chronic motor complete spinal cord injury (SCI).DesignCase series.MethodsSeven adult men with chronic (≥2 years), thoracic motor complete (AIS A–B) SCI completed a 40-week course of thrice-weekly intermittent PS-WBV therapy, in a flexed knee posture (160°), for 45 minutes per session at a frequency of 45 Hz and 0.6–0.7 mm displacement using the WAVE® Pro Plate, with an integrated EasyStand™ standing frame. EMG was measured in major lower extremity muscles to represent muscle activity during PS-WBV. The cross-sectional area and density of the calf muscles were measured using peripheral quantitative computed tomography at the widest calf cross-section (66% of the tibia length) at pre- and post-intervention. All measured variables were compared between the pre- and post-intervention measurements to assess change after the PS-WBV intervention.ResultsPS-WBV acutely induced EMG activity in lower extremity muscles of SCI subjects. No significant changes in lower extremity EMG activity, muscle cross-sectional area, or density were observed following the 40-week intervention.ConclusionsAlthough acute exposure to PS-WBV can induce electrophysiological activity of lower extremity muscles during PS in men with motor complete SCI, the PS-WBV intervention for 40 weeks was not sufficient to result in enhanced muscle activity, or to increase calf muscle cross-sectional area or density.

H‐reflexes reduce fatigue of evoked contractions after spinal cord injury

Neuromuscular electrical stimulation (NMES) over a muscle belly (mNMES) generates contractions predominantly through M-waves, while NMES over a nerve trunk (nNMES) can generate contractions through H-reflexes in people who are neurologically intact. We tested whether the differences between mNMES and nNMES are present in people with chronic motor-complete spinal cord injury and, if so, whether they influence contraction fatigue. Plantar-flexion torque and soleus electromyography were recorded from 8 participants. Fatigue protocols were delivered using mNMES and nNMES on separate days. nNMES generated contractions that fatigued less than mNMES. Torque decreased the least when nNMES generated contractions, at least partly through H-reflexes (n = 4 participants; 39% decrease), and torque decreased the most when contractions were generated through M-waves, regardless of NMES site (nNMES 71% decrease, n = 4; mNMES, 73% decrease, n = 8). nNMES generates contractions that fatigue less than mNMES, but only when H-reflexes contribute to the evoked contractions.

Safety of Granulocyte Colony-Stimulating Factor (G-CSF) Administration for Postrehabilitated Motor Complete Spinal Cord Injury Patients: An Open-Label, Phase I Study

Granulocyte colony-stimulating factor (G-CSF) is a major growth factor in the activation and differentiation of granulocytes. This cytokine has been widely and safely employed in different conditions over many years. In this translational study, G-CSF is administered to 19 patients with chronic motor complete spinal cord injury, and outcomes are reported. All 19 patients received subcutaneous G-CSF (5 µg/kg per day) for 5 days and were followed for at least 6 months. The American Spinal Injury Association (ASIA) scale was used for motor and sensory assessment, and the International Association of Neurorestoratology-Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS) and the Spinal Cord Independence Measure (SCIM) III were used to assess improvements in the ability to perform basic daily tasks. At the 6-month follow-up, upper extremity motor scores improved by 10, which was statistically significant (p = 0.007), whereas there were no significant changes in lower extremity motor scores. Also, the median of light touch sensory scores improved by 5 (p = 0.001). Pinprick sensory scores significantly improved (p = 0.002). The median increment in SCIM III total score was 7 (p = 0.001). The improvements in bladder and bowel management as well as moderate distance mobility subscales were also significant (p < 0.05). Total IANR-SCIFRS scores changed from 17 to 32, which was statistically significant (p = 0.001); again the bladder and bowel management subscale improvements were statistically significant (p < 0.05). Mild side effects of the G-CSF treatment such as bone pain, rash, fever, neuropathic pain, and spasticity were noted in a few patients; all of them resolved after 1 week. Our results indicate that G-CSF administration is a safe process and is associated with neurological as well as functional improvement. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Recovery of assisted overground stepping in a patient with chronic motor complete spinal cord injury: A case report

Clinical studies have shown that after incomplete spinal cord lesions at the thoracic level, patients can develop functional gait patterns through gait training. To date, however, training has been ineffective in producing gait in patients with clinically motor complete spinal cord lesions. Here we report a patient with chronic motor complete spinal cord injury who regained locomotor function with assistance after intensive gait rehabilitation treatment. A fifteen year old female patient had sustained motor complete spinal cord injury (T6, AIS B) 2 years earlier, with severe bilateral extensor spasticity, and ineffective previous gait training with robotic systems. The therapy consisted of two months of gait training with a robotic system combined with bilateral functional electrical stimulation (FES) of the peroneal nerve, and one month of gait training with a special walker and FES of the left leg and occasionally on the right leg, due to flexor reflex could sometimes be initiated by the patient in the right leg without electrical stimulation. Neurophysiological studies and ten metres test were done. At the end of training, the patient was able to cover a distance of 200 metres without FES with a walker and assistance from a physiotherapist, who pulled the walker with each step to help her to accomplish effective overground stepping. Motor and somatosensory evoked potentials were absent in the lower limbs. Even after a motor complete lesion with some preservation of sensory pathways, the spinal cord may be able to retain some of its locomotor function through intensive gait rehabilitation.

Relationship of Spasticity to Soft Tissue Body Composition and the Metabolic Profile in Persons With Chronic Motor Complete Spinal Cord Injury

Background/Objective: To determine the effects of spasticity on anthropometrics, body composition (fat mass [FM] and fat-free mass [FFM]), and metabolic profile (energy expenditure, plasma glucose, insulin concentration, and lipid panel) in individuals with motor complete spinal cord injury (SCI).Methods: Ten individuals with chronic motor complete SCI (age, 33 ± 7 years; BMI, 24 ± 4 kg/m2; level of injury, C6—T11; American Spinal Injury Association A and B) underwent waist and abdominal circumferences to measure trunk adiposity. After the first visit, the participants were admitted to the general clinical research center for body composition (FFM and FM) assessment using dual energy x-ray absorptiometry. After overnight fasting, resting metabolic rate (RMR) and metabolic profile (plasma glucose, insulin, and lipid profile) were measured. Spasticity of the hip, knee, and ankle flexors and extensors was measured at 6 time points over 24 hours using the Modified Ashworth Scale.Results: Knee extensor spasticity was negatively correlated to abdominal circumferences (r = -0.66, P = 0.038). After accounting for leg or total FFM, spasticity was negatively related to abdominal circumference (r = -0.67, P = 0.03). Knee extensor spasticity was associated with greater total %FFM (r = 0.64; P = 0.048), lower %FM (r = -0.66; P = 0.03), and lower FM to FFM ratio. Increased FFM (kg) was associated with higher RMR (r = 0.89; P = 0.0001). Finally, spasticity may indirectly influence glucose homeostasis and lipid profile by maintaining FFM (r = -0.5 to -0.8, P < 0.001).Conclusion: Significant relationships were noted between spasticity and variables of body composition and metabolic profile in persons with chronic motor complete SCI, suggesting that spasticity may play a role in the defense against deterioration in these variables years after injury. The exact mechanism is yet to be determined.