Bone changes in the lower limbs from participation in an FES rowing exercise program implemented within two years after traumatic spinal cord injury.

Objective: To determine the effect of a functional electrical stimulation (FES) rowing program on bone mineral density (BMD) when implemented within two years after SCI.Design: Prospective.Setting: Health Care Facility.Participants: Convenience sample; four adults with recent (<2 years) traumatic, motor complete SCI (C7-T12 AIS A-B).Intervention: A 90-session FES rowing exercise program; participants attended 30-minute FES training sessions approximately three times each week for the duration of their participation.Outcome Measures: BMD in the distal femur and tibia were measured using peripheral Quantitative Computed Tomography (pQCT) at enrollment (T0) and after 30 (T1), 60 (T2), and 90 (T3) sessions. Bone stimulus was calculated for each rower at each time point using the average number of weekly loading cycles, peak foot reaction force, and bone mineral content from the previous time point. A regression analysis was used to determine the relationship between calculated bone stimulus and change in femoral trabecular BMD between time points.Results: Trabecular BMD in the femur and tibia decreased for all participants in T0-1, but the rate of loss slowed or reversed between T1-2, with little-to-no bone loss for most participants during T2-3. The calculated bone stimulus was significantly correlated with change in femoral trabecular BMD (P = 0.016; R2 = 0.458).Conclusion: Consistent participation in an FES rowing program provides sufficient forces and loading cycles to reduce or reverse expected bone loss at the distal femur and tibia, at least temporarily, in some individuals within two years after SCI.Trial Registration: NCT02008149.

Genital nerve stimulation increases bladder capacity after SCI: A meta-analysis.

BACKGROUND: Neurogenic detrusor overactivity (NDO) often results in decreased bladder capacity, urinary incontinence, and vesico-ureteral reflux. NDO can trigger autonomic dysreflexia and can impair quality of life. Electrical stimulation of the genital nerves (GNS) acutely inhibits reflex bladder contractions and can increase bladder capacity. Quantifying the effect of GNS on bladder capacity and determining what study factors and subject factors influence bladder capacity improvements will inform the design of clinical GNS interventions. METHODS: We measured bladder capacity in 33 individuals with NDO, with and without GNS. These data were combined with data from seven previous GNS studies (n=64 subjects). A meta-analysis of the increase in bladder capacity and potential experimental factors was conducted (n=97 subjects total). RESULTS: Bladder capacity increased 131±101 ml with GNS across subjects in all studies. The number of individuals whose bladder capacity was greater than 300 ml increased from 24% to 62% with GNS. Stimulus amplitude was a significant factor predicting bladder capacity gain. The variance of the bladder capacity gain significantly increased with increasing infusion rate. Other factors did not contribute to bladder capacity gain. CONCLUSION: GNS acutely increases bladder capacity in individuals with NDO. The consistent increase in magnitude of bladder capacities across the eight studies, and the lack of dependence on individual-specific factors, provide confidence that GNS could be an effective tool for many individuals with NDO. Studies of the chronic effect of GNS on bladder control, with clinical measures such as urinary continence, are needed.

Traumatic brain injury in U.S. Veterans with traumatic spinal cord injury.

Patients with both a spinal cord injury (SCI) and traumatic brain injury (TBI) are often very difficult to manage and can strain the resources of clinical units specialized in treating either diagnosis. However, a wide range of estimates exists on the extent of this problem. The aim of this study was to describe the scope of the problem in a well-defined population attending a comprehensive SCI unit. Electronic medical records of all patients with SCI being followed by the SCI unit in a U.S. Veterans' hospital were searched to identify those with concurrent TBI. The data were analyzed for age, sex, cause of injury, level and completeness of SCI, cognitive impairment, relationship with Active Duty military, and date of injury. Of 409 Veterans with a traumatic SCI, 99 (24.2%) were identified as having had a concurrent TBI. The occurrence did not appear to be closely related to military conflict. Reports of TBI were much more common in the last 20 yr than in previous decades. Documentation of TBI in patients with SCI was inconsistent. Improved screening and documentation could identify all patients with this dual diagnosis and facilitate appropriate management.

Neural Placode Tissue Derived From Myelomeningocele Repair Serves as a Viable Source of Oligodendrocyte Progenitor Cells.

BACKGROUND: The presence, characteristics, and potential clinical relevance of neural progenitor populations within the neural placodes of myelomeningocele patients remain to be studied. Neural stem cells are known to reside adjacent to ependyma-lined surfaces along the central nervous system axis. OBJECTIVE: Given such neuroanatomic correlation and regenerative capacity in fetal development, we assessed myelomeningocele-derived neural placode tissue as a potentially novel source of neural stem and progenitor cells. METHODS: Nonfunctional neural placode tissue was harvested from infants during the surgical repair of myelomeningocele and subsequently further analyzed by in vitro studies, flow cytometry, and immunofluorescence. To assess lineage potential, neural placode-derived neurospheres were subjected to differential media conditions. Through assessment of platelet-derived growth factor receptor α (PDGFRα) and CD15 cell marker expression, Sox2+Olig2+ putative oligodendrocyte progenitor cells were successfully isolated. RESULTS: PDGFRαCD15 cell populations demonstrated the highest rate of self-renewal capacity and multipotency of cell progeny. Immunofluorescence of neural placode-derived neurospheres demonstrated preferential expression of the oligodendrocyte progenitor marker, CNPase, whereas differentiation to neurons and astrocytes was also noted, albeit to a limited degree. CONCLUSION: Neural placode tissue contains multipotent progenitors that are preferentially biased toward oligodendrocyte progenitor cell differentiation and presents a novel source of such cells for use in the treatment of a variety of pediatric and adult neurological disease, including spinal cord injury, multiple sclerosis, and metabolic leukoencephalopathies.

Consistency among musculoskeletal models: caveat utilitor.

Musculoskeletal simulation software and model repositories have broadened the user base able to perform musculoskeletal analysis and have facilitated in the sharing of models. As the recognition of musculoskeletal modeling continues to grow as an engineering discipline, the consistency in results derived from different models and software is becoming more critical. The purpose of this study was to compare eight models from three software packages and evaluate differences in quadriceps moment arms, predicted muscle forces, and predicted tibiofemoral contact forces for an idealized knee-extension task spanning -125 to +10° of knee extension. Substantial variation among models was observed for the majority of aspects evaluated. Differences among models were influenced by knee angle, with better agreement of moment arms and tibiofemoral joint contact force occurring at low to moderate knee flexion angles. The results suggest a lack of consistency among models and that output differences are not simply an artifact of naturally occurring inter-individual differences. Although generic musculoskeletal models can easily be scaled to consistent limb lengths and use the same muscle recruitment algorithm, the results suggest those are not sufficient conditions to produce consistent muscle or joint contact forces, even for simplified models with no potential of co-contraction.

Combined SCI and TBI: recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement.

A significant proportion (estimates range from 16 to 74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI+TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6weeks, in the paw placement test, SCI+contralateral TBI produced a profound deficit that failed to recover, but SCI+ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI+contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI+contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the contralateral hemisphere in all tests, but forepaw placements were relatively increased by an ipsilateral TBI relative to SCI alone, perhaps due to the dual competing injuries influencing the use of both forelimbs. These findings emphasize the complexity of recovery from combined CNS injuries, and the possible role of plasticity and laterality in rehabilitation, and provide a start towards a useful preclinical model for evaluating effective therapies for combine SCI and TBI.

Functional electrical stimulation for bladder, bowel, and sexual function.

The principles of using electrical stimulation of peripheral nerves or nerve roots for restoring useful bladder, bowel, and sexual function after damage or disease of the central nervous system are described. Activation of somatic or parasympathetic efferent nerves can produce contraction of striated or smooth muscle in the bladder, rectum, and sphincters. Activation of afferent nerves can produce reflex activation of somatic muscle and reflex inhibition or activation of smooth muscle in these organs. In clinical practice these techniques have been used to produce effective emptying of the bladder and bowel in patients with spinal cord injury and to improve continence of urine and feces. Stimulation of parasympathetic efferents can produce sustained erection of the penis, and stimulation of the nerves to the seminal vesicles can produce seminal emission. Reflex erection and ejaculation can also be produced by stimulation of afferent nerves. Experimental techniques for controlling emptying and continence by a single device, and prospects for comprehensive control of bladder, bowel, and sexual function by electrical techniques are described. These may include more selective electrodes, inactivation of nerves by specific stimulus parameters, greater use of sensors, and networking of implanted components connected to the central and peripheral nervous system.

Lower thoracic spinal cord stimulation to restore cough in patients with spinal cord injury: results of a National Institutes of Health-Sponsored clinical trial. Part II: clinical outcomes.

OBJECTIVE: To evaluate the clinical effects of spinal cord stimulation (SCS) to restore cough in subjects with cervical spinal cord injury. DESIGN: Clinical trial assessing the clinical outcomes and side effects associated with the cough system. SETTING: Outpatient hospital or residence. PARTICIPANTS: Subjects (N=9; 8 men, 1 woman) with cervical spinal cord injury. INTERVENTIONS: SCS was performed at home by either the subjects themselves or caregivers on a chronic basis and as needed for secretion management. MAIN OUTCOME MEASURES: Ease in raising secretions, requirement for trained caregiver support related to secretion management, and incidence of acute respiratory tract infections. RESULTS: The degree of difficulty in raising secretions improved markedly, and the need for alternative methods of secretion removal was virtually eliminated. Subject life quality related to respiratory care improved, with subjects reporting greater control of breathing problems and enhanced mobility. The incidence of acute respiratory tract infections fell from 2.0+/-0.5 to 0.7+/-0.4 events/subject year (P<.01), and mean level of trained caregiver support related to secretion management measured over a 2-week period decreased from 16.9+/-7.9 to 2.1+/-1.6 and 0.4+/-0.3 times/wk (P<.01) at 28 and 40 weeks after implantation of the device, respectively. Three subjects developed mild hemodynamic effects that abated completely with continued SCS. Subjects experienced mild leg jerks during SCS, which were well tolerated. There were no instances of bowel or bladder leakage. CONCLUSIONS: Restoration of cough via SCS is safe and efficacious. This method improves life quality and has the potential to reduce the morbidity and mortality associated with recurrent respiratory tract infections in this patient population.

Selective activation of the sacral anterior roots for induction of bladder voiding.

AIM: We investigated the efficacy of selective activation of the smaller diameter axons in the sacral anterior roots for electrically induced bladder voiding. MATERIALS AND METHODS: Acute experiments were conducted in five adult dogs. The anterior sacral roots S2 and S3 were implanted bilaterally with tripolar electrodes. Pressures were recorded from the bladder and from the proximal urethra and the external urethral sphincter. A detector and flow meter monitored fluid flow. A complete sacral dorsal rhizotomy was carried out. The effects of two types of pulse trains at 20 Hz were compared; quasitrapezoidal pulses (500 microsec with 500 microsec exponential decay) and interrupted rectangular (100 microsec, 2 sec on/2 sec off). Before rhizotomy, rectangular pulse trains (100 microsec) to activate all fibers were also applied. The experimental design was block randomized before and after rhizotomy. RESULTS: Quasitrapezoidal pulses showed block of sphincter activation with average minimum current for maximum suppression of 1.37 mA. All pulse types evoked average bladder pressures above the basal sphincter closure pressure. The pressure patterns in the proximal urethra closely followed the bladder pressures. Before dorsal rhizotomy, stimulation evoked a superadded increase in sphincter pressures with slow rise time. After rhizotomy, the sphincter pressure patterns followed the bladder pressures during selective activation and voiding occurred during stimulation with quasitrapezoidal trains and in between bursts with interrupted rectangular stimulation. CONCLUSIONS: Selective activation of sacral ventral roots combined with dorsal rhizotomy may provide a viable means of low-pressure continuous voiding in neurological impairment.

Detection of neurogenic detrusor contractions from the activity of the external anal sphincter in cat and human.

AIMS: Individuals with spinal cord injury or neurological disorders may develop bladder contractions at low volumes (neurogenic detrusor overactivity), which can lead to significant health problems. Present devices can inhibit unwanted contractions through continuous electrical stimulation of sensory nerves, but do not enable conditional stimulation only at the onset of bladder contractions. The objectives of this study were to determine the relationship between the electrical activity of external anal sphincter (EAS) and bladder pressure during neurogenic detrusor contractions and to determine whether EAS activity could be used to detect the onset of bladder contractions. METHODS: Bladder pressure and EAS electromyogram (EMG) were recorded in nine adult male cats. Retrospective clinical data consisting of bladder pressure and EAS EMG from 41 spinal cord injured individuals with neurogenic detrusor overactivity were analyzed. A CUSUM algorithm was used to detect the onset of bladder contractions from the EAS EMG. RESULTS: EAS EMG activity increased at the onset of bladder contractions in six cats (dyssynergic) and decreased (synergic) in three cats. The onset of bladder contractions was detected within 3 sec of the start of the contraction for both the synergic and dyssynergic data sets. The onset of bladder contractions was detected within 1 sec of the start of the bladder contraction for both synergic and dyssynergic human subjects. CONCLUSIONS: Recordings of the EAS EMG can be used to detect robustly the onset of neurogenic detrusor contractions. The EAS EMG is a suitable signal to control closed-loop inhibitory electrical stimulation to maintain urinary continence.

Clinical applications of electrical stimulation after spinal cord injury.

During the last one-half century, electrical stimulation has become clinically significant for improving health and restoring useful function after spinal cord injury. Short-term stimulation can be provided by electrodes on the skin or percutaneous fine wires, but implanted systems are preferable for long-term use. Electrical stimulation of intact lower motor neurons can exercise paralyzed muscles and reverse wasting; improve strength, endurance, and cardiovascular fitness; and may reduce the progression of osteoporosis. Other potential therapeutic uses being investigated include reduction of spasticity, prevention of deep vein thrombosis, and improvement of tissue health. Pacing of intact phrenic nerves in high tetraplegia can produce effective respiration without mechanical ventilation, allowing improved speech, increased mobility, and increased sense of well-being. Improvement of cough has also been demonstrated. Stimulation of intact sacral nerves can produce effective micturition and reduce urinary tract infection; it can also improve bowel function and erection. It is usually combined with posterior sacral rhizotomy to improve continence and bladder capacity, and the combination has been shown to reduce costs of care. Electroejaculation can now produce semen in most men with spinal cord injury. Significant achievements have also been made in restoring limb function. Useful hand grasp can be provided in C5 and C6 tetraplegia, reducing dependence on adapted equipment and assistants. Standing, assistance with transfers, and walking for short distances can be provided to selected persons with paraplegia, improving their access to objects, places, and opportunities that are inaccessible from a wheelchair. This review summarizes the current state of therapeutic and neuroprosthetic applications of electrical stimulation after spinal cord injury and identifies some future directions of research and clinical and commercial development.

Difficulty with evacuation after spinal cord injury: colonic motility during sleep and effects of abdominal wall stimulation.

Difficulty with evacuation (DWE) is common in individuals with spinal cord injury (SCI). Numerous studies have concluded that constipation, impaction, and incontinence cause significant morbidity and, collectively, constitute an important quality-of-life issue in individuals with SCI. Colonic motor activity was assessed using a solid-state manometry probe. We report here that colonic pressure activity is depressed during sleep compared to that observed in able-bodied controls. In addition, pressure activity was decreased during sleep compared to pre-sleep and post-sleep. We suspect that this may contribute to delayed colon transit time after SCI. In addition, since contraction of the abdominal wall musculature plays a role in normal defecation, we assessed whether an abdominal belt with implanted electrodes would improve DWE. In this respect, we demonstrated that neuromuscular stimulation of the abdominal wall improves a number of indices of defecatory function, including time to first stool and total bowel care time.

A urethral afferent mediated excitatory bladder reflex exists in humans.

An excitatory reflex between urethral flow receptors and the bladder has been established in animals, but attempts to demonstrate this reflex in humans using urethral fluid flow have been inconclusive. Intraurethral electrical stimulation has recently been shown to generate bladder contractions in animals and was applied to study the presence of an excitatory urethra to bladder reflex in humans. The prostatic urethra was stimulated electrically via a catheter-based electrode in five men with complete spinal cord injury. Bladder contractions were generated in four of five individuals, however, only when the bladder volume was sufficiently large. These results demonstrate the presence of a volume dependent excitatory bladder reflex mediated by urethral afferent nerve fibers and the lumbosacral spinal cord.

A catheter based method to activate urethral sensory nerve fibers.

PURPOSE: The ability to control bladder activity would provide a valuable tool to assist individuals with neurological disorders or spinal cord injury (SCI). Recent studies in animal models have shown that bladder contractions can be evoked by electrical stimulation of urethral afferent nerves. We developed and validated in cats a minimally invasive method to stimulate electrically the sensory nerve fibers that innervate the urethra. MATERIALS AND METHODS: The urethra was stimulated electrically along its length via a catheter mounted circumferential electrode in 6 cats. The urethra was similarly stimulated in a male individual with complete SCI. RESULTS: Robust bladder contractions were generated via intraurethral electrical stimulation in all cat experiments. Peak responses were obtained in the proximal and prostatic urethra. In the individual with SCI bladder contractions were generated via intraurethral stimulation at a position 4 cm distal to the bladder. Responses in cats and the human depended on bladder volume. CONCLUSIONS: To our knowledge this study provides the first documentation of generating bladder contractions via intraurethral electrical stimulation in cats and humans. This method provides a research tool for future studies to investigate these pathways in humans. Preliminary human results suggest that urethral afferent mediated neural pathways demonstrated in animal models exist in humans and support the development of neural prostheses using electrical stimulation of these nerves to restore control of bladder function in individuals with neurological disorders or SCI.

Detrusor and blood pressure responses to dorsal penile nerve stimulation during hyperreflexic contraction of the bladder in patients with cervical cord injury.

OBJECTIVE: To investigate the immediate effect of dorsal penile nerve (DPN) stimulation on detrusor pressure (P(det)) and blood pressure during hyperreflexic contractions of the bladder in patients with cervical spinal cord injury (SCI). DESIGN: Blood pressure and P(det) monitoring during cystometry with and without DPN stimulation. SETTING: Urodynamic laboratory in a university hospital in Korea. PARTICIPANTS: Eight men (age range, 20-55y) with cervical SCI that was incurred from 4 months to 10 years before this study. INTERVENTION: During water cystometry, blood pressure was monitored with an intra-arterial catheter introduced percutaneously into the radial artery and was recorded simultaneously with the P(det). Blood pressure was also measured manually with an electronic blood pressure cuff. Electric stimulation was applied to the DPN by using surface electrodes each time a bladder contraction was detected. Stimulation intensity was twice the threshold of the pudendal-anal reflex. MAIN OUTCOME MEASURES: P(det), systolic blood pressure, and diastolic blood pressure. RESULTS: As P(det) increased, the blood pressure increased in all cases. All the reflex contractions of the bladder were effectively suppressed by DPN stimulation, and as the P(det) decreased during stimulation, radial arterial pressure also decreased immediately and significantly. CONCLUSIONS: DPN stimulation can decrease P(det) and the increased blood pressure associated with it.

Self-controlled dorsal penile nerve stimulation to inhibit bladder hyperreflexia in incomplete spinal cord injury: a case report.

Intermittent catheterization is not always successful in achieving continence in spinal cord injury (SCI) and often requires adjunctive methods. Electric stimulation of sacral afferent nerves reduces hyperactivity of the bladder. This report describes application of self-controlled dorsal penile nerve stimulation for bladder hyperreflexia in incomplete SCI. The patient was a 33-year-old man with C6 incomplete quadriplegia who managed his bladder with intermittent self-catheterization and medication. Despite this, he continued to have reflex bladder contractions that he could feel but could not catheterize himself in time to prevent incontinence. We performed cystometry with dorsal penile nerve stimulation and analyzed data of home use of stimulation. During cystometry, the suppressive effect of electric stimulation on hyperreflexic contractions was reliable and reproducible. The patient could start stimulation on sensing bladder contraction, and the suppression of reflex contraction lasted several minutes after stopping brief stimulation. When using stimulation at home, the rate of leakage between catheterization decreased, and catheterized volume increased significantly.