Effect of Different Forms of Activity-Based Recovery Training on Bladder, Bowel, and Sexual Function After Spinal Cord Injury.

OBJECTIVES: To investigate whether the urogenital and bowel functional gains previously demonstrated post-locomotor step training after chronic spinal cord injury could have been derived due to weight-bearing alone or from exercise in general. DESIGN: Prospective cohort study; pilot trial with small sample size. SETTING: Urogenital and bowel scientific core facility at a rehabilitation institute and spinal cord injury research center in the United States. PARTICIPANTS: Men and women (N=22) with spinal cord injury (American Spinal Injury Association Impairment Scale grades of A-D) participated in this study. INTERVENTIONS: Approximately 80 daily 1-hour sessions of either stand training or nonweight-bearing arm crank ergometry. Comparisons were made with previously published locomotor training data (step; N=7). MAIN OUTCOME MEASURES: Assessments at both pre- and post-training timepoints included cystometry for bladder function and International Data Set Questionnaires for bowel and sexual functions. RESULTS: Cystometry measurements revealed a significant decrease in bladder pressure and limited improvement in compliance with nonweight-bearing exercise but not with standing. Although International Data Set questionnaires revealed profound bowel dysfunction and marked deficits in sexual function pretraining, no differences were identified poststand or after nonweight-bearing exercise. CONCLUSIONS: These pilot trial results suggest that, although stand and weight-bearing alone do not benefit pelvic organ functions after spinal cord injury, exercise in general may contribute at least partially to the lowering of bladder pressure and the increase in compliance that was seen previously with locomotor training, potentially through metabolic, humoral, and/or cardiovascular mechanisms. Thus, to maximize activity-based recovery training benefits for functions related to storage and emptying, an appropriate level of sensory input to the spinal cord neural circuitries controlling bladder and bowel requires task-specific stepping.

Effects of NMES pulse width and intensity on muscle mechanical output and oxygen extraction in able-bodied and paraplegic individuals.

PURPOSE: Neuromuscular Electrical Stimulation (NMES) is commonly used in neuromuscular rehabilitation protocols, and its parameters selection substantially affects the characteristics of muscle activation. Here, we investigated the effects of short pulse width (200 µs) and higher intensity (short-high) NMES or long pulse width (1000 µs) and lower intensity (long-low) NMES on muscle mechanical output and fractional oxygen extraction. Muscle contractions were elicited with 100 Hz stimulation frequency, and the initial torque output was matched by adjusting stimulation intensity. METHODS: Fourteen able-bodied and six spinal cord-injured (SCI) individuals participated in the study. The NMES protocol (75 isometric contractions, 1-s on-3-s off) targeting the knee extensors was performed with long-low or short-high NMES applied over the midline between anterior superior iliac spine and patella protrusion in two different days. Muscle work was estimated by torque-time integral, contractile properties by rate of torque development and half-relaxation time, and vastus lateralis fractional oxygen extraction was assessed by Near-Infrared Spectroscopy (NIRS). RESULTS: Torque-time integral elicited by the two NMES paradigms was similar throughout the stimulation protocol, with differences ranging between 1.4% (p = 0.877; able-bodied, mid-part of the protocol) and 9.9% (p = 0.147; SCI, mid-part of the protocol). Contractile properties were also comparable in the two NMES paradigms. However, long-low NMES resulted in higher fractional oxygen extraction in able-bodied (+ 36%; p = 0.006). CONCLUSION: Long-low and short-high NMES recruited quadriceps femoris motor units that demonstrated similar contractile and fatigability properties. However, long-low NMES conceivably resulted in the preferential recruitment of vastus lateralis muscle fibers as detected by NIRS.

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

NEW FINDINGS: 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. ABSTRACT: 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 (7 days week-1 ; 2 h day-1 in four individuals and 5 h day-1 in two individuals) over a period of ∼6 months significantly increased lower limb lean mass (by 0.67 ± 0.39 kg 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 44 N m 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.

Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study.

BACKGROUND: Repeated periods of stimulation of the spinal cord and training increased the ability to control movement in animal models of spinal cord injury. We hypothesised that tonic epidural spinal cord stimulation can modulate spinal circuitry in human beings into a physiological state that enables sensory input from standing and stepping movements to serve as a source of neural control to undertake these tasks. METHODS: A 23-year-old man who had paraplegia from a C7-T1 subluxation as a result of a motor vehicle accident in July 2006, presented with complete loss of clinically detectable voluntary motor function and partial preservation of sensation below the T1 cord segment. After 170 locomotor training sessions over 26 months, a 16-electrode array was surgically placed on the dura (L1-S1 cord segments) in December 2009, to allow for chronic electrical stimulation. Spinal cord stimulation was done during sessions that lasted up to 250 min. We did 29 experiments and tested several stimulation combinations and parameters with the aim of the patient achieving standing and stepping. FINDINGS: Epidural stimulation enabled the man to achieve full weight-bearing standing with assistance provided only for balance for 4·25 min. The patient achieved this standing during stimulation using parameters identified as specific for standing while providing bilateral load-bearing proprioceptive input. We also noted locomotor-like patterns when stimulation parameters were optimised for stepping. Additionally, 7 months after implantation, the patient recovered supraspinal control of some leg movements, but only during epidural stimulation. INTERPRETATION: Task-specific training with epidural stimulation might reactivate previously silent spared neural circuits or promote plasticity. These interventions could be a viable clinical approach for functional recovery after severe paralysis. FUNDING: National Institutes of Health and Christopher and Dana Reeve Foundation.

Correction: Novel stochastic framework for automatic segmentation of human thigh MRI volumes and its applications in spinal cord injured individuals.

[This corrects the article DOI: 10.1371/journal.pone.0216487.].

Novel stochastic framework for automatic segmentation of human thigh MRI volumes and its applications in spinal cord injured individuals.

Severe spinal cord injury (SCI) leads to skeletal muscle atrophy and adipose tissue infiltration in the skeletal muscle, which can result in compromised muscle mechanical output and lead to health-related complications. In this study, we developed a novel automatic 3-D approach for volumetric segmentation and quantitative assessment of thigh Magnetic Resonance Imaging (MRI) volumes in individuals with chronic SCI as well as non-disabled individuals. In this framework, subcutaneous adipose tissue, inter-muscular adipose tissue and total muscle tissue are segmented using linear combination of discrete Gaussians algorithm. Also, three thigh muscle groups were segmented utilizing the proposed 3-D Joint Markov Gibbs Random Field model that integrates first order appearance model, spatial information, and shape model to localize the muscle groups. The accuracy of the automatic segmentation method was tested both on SCI (N = 16) and on non-disabled (N = 14) individuals, showing an overall 0.93±0.06 accuracy for adipose tissue and muscle compartments segmentation based on Dice Similarity Coefficient. The proposed framework for muscle compartment segmentation showed an overall higher accuracy compared to ANTs and STAPLE, two previously validated atlas-based segmentation methods. Also, the framework proposed in this study showed similar Dice accuracy and better Hausdorff distance measure to that obtained using DeepMedic Convolutional Neural Network structure, a well-known deep learning network for 3-D medical image segmentation. The automatic segmentation method proposed in this study can provide fast and accurate quantification of adipose and muscle tissues, which have important health and functional implications in the SCI population.

Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury.

OBJECTIVE: Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs' pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). STUDY DESIGN: Prospective cohort study; pilot trial with small sample size. METHODS: Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. RESULTS: Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. CONCLUSIONS: These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03036527.

Novel multi-system functional gains via task specific training in spinal cord injured male rats.

Locomotor training (LT) after spinal cord injury (SCI) is a rehabilitative therapy used to enhance locomotor recovery. There is evidence, primarily anecdotal, also associating LT with improvements in bladder function and reduction in some types of SCI-related pain. In the present study, we determined if a step training paradigm could improve outcome measures of locomotion, bladder function, and pain/allodynia. After a T10 contusive SCI trained animals (adult male Wistar rats), trained animals began quadrupedal step training beginning 2 weeks post-SCI for 1 h/day. End of study experiments (3 months of training) revealed significant changes in limb kinematics, gait, and hindlimb flexor-extensor bursting patterns relative to non-trained controls. Importantly, micturition function, evaluated with terminal transvesical cystometry, was significantly improved in the step trained group (increased voiding efficiency, intercontraction interval, and contraction amplitude). Because both SCI and LT affect neurotrophin signaling, and neurotrophins are involved with post-SCI plasticity in micturition pathways, we measured bladder neurotrophin mRNA. Training regulated the expression of nerve growth factor (NGF) but not BDNF or NT3. Bladder NGF mRNA levels were inversely related to bladder function in the trained group. Monitoring of overground locomotion and neuropathic pain throughout the study revealed significant improvements, beginning after 3 weeks of training, which in both cases remained consistent for the study duration. These novel findings, improving non-locomotor in addition to locomotor functions, demonstrate that step training post-SCI could contribute to multiple quality of life gains, targeting patient-centered high priority deficits.