Electrical stimulation of sacral nerves and roots for control of the neurogenic bladder and bowel.

After damage to the spinal cord, some of the most frequent and severe complications are due to the neurogenic bladder and bowel, in spite of a variety of methods of management. Bladder and bowel emptying is usually impaired, but electrical stimulation of nerves surviving after spinal cord injury can produce controlled contraction of muscle, including the smooth muscle of the bladder and lower bowel, and this can be used to produce safe and effective bladder emptying on demand without catheters. It can also aid emptying of the bowel and reduce constipation. Hyper-reflexia of the bladder and lower bowel after spinal cord injury can produce reflex incontinence of urine and stool, and while this can sometimes be reduced by neuromodulation, it can be more predictably reduced by rhizotomy of the sacral sensory roots, while preserving the motor roots for stimulation. This combination of electrical stimulation and rhizotomy has restored bladder and bowel emptying and continence to several thousand patients, with reduced complications and improved quality of life over many years.

Adapting the Finetech-Brindley Sacral Anterior Root Stimulator for Bioelectronic Medicine.

The Finetech-Brindley Sacral Anterior Root Stimulator (SARS) is a low cost and reliable system. The architecture has been used for various bioelectric treatments, including several thousand implanted systems for restoring bladder function following spinal cord injury (SCI). Extending the operational frequency range would expand the capability of the system; enabling, for example, the exploration of eliminating the rhizotomy through an electrical nerve block. The distributed architecture of the SARS system enables stimulation parameters to be adjusted without modifying the implant design or manufacturing. To explore the design degrees-of-freedom, a circuit simulation was created and validated using a modified SARS system that supported stimulation frequencies up to 600 Hz. The simulation was also used to explore high frequency (up to 30kHz) behaviour, and to determine the constraints on charge delivered at the higher rates. A key constraint found was the DC blocking capacitors, designed originally for low frequency operation, not fully discharging within a shortened stimulation period. Within these current implant constraints, we demonstrate the potential capability for higher frequency operation that is consistent with presynaptic stimulation block, and also define targeted circuit improvements for future extension of stimulation capability.

Needs, priorities, and attitudes of individuals with spinal cord injury toward nerve stimulation devices for bladder and bowel function: a survey.

STUDY DESIGN: Survey. OBJECTIVES: To investigate the needs and priorities of people with spinal cord injury for managing neurogenic bladder and bowel function and to determine their willingness to adopt neuromodulation interventions for these functions. METHODS: Anonymous online survey. It was advertised by word-of-mouth by community influencers and social media, and by advertisement in newsletters of advocacy groups. RESULTS: Responses from 370 individuals (27% female, 73% male) were included. Bladder emptying without catheters was the top priority for restoring bladder function, and maintaining fecal continence was the top priority for restoring bowel function. The biggest concerns regarding external stimulation systems were wearing a device with wires connecting to electrodes on the skin and having to don and doff the system daily as needed. The biggest concerns for implanted systems were the chances of experiencing problems with the implant that required a revision surgery or surgical removal of the whole system. Respondents were willing to accept an external (61%) or implanted (41%) device to achieve improved bladder or bowel function. CONCLUSIONS: Bladder and bowel dysfunction remain important unmet challenges for individuals living with SCI who answered our survey. These individuals are willing to accept some potential risks of nerve stimulation approaches given potential benefits. Additional consumer input is critical for guiding both research and translation to clinical use and personalized medicine.

Implantation of Sacral Nerve Stimulator Without Rhizotomy for Neurogenic Bladder in Patient With Spinal Cord Injury: 2-Dimensional Operative Video.

There are approximately 12 000 new individuals with spinal cord injury (SCI) each year, and close to 200 000 individuals live with a SCI-related disability in the United States. The majority of patients with SCI have bladder dysfunction as a result of their injury, with over 75% unable to void volitionally following their injury. In patients with traumatic SCI, intermittent catheterization is commonly recommended, but a lack of adherence to clean intermittent catheterization (CIC) has been observed, with up to 50% discontinuing CIC within 5 yr of injury. The Finetech Brindley Bladder System (FBBS) is an implantable sacral nerve stimulator for improving bladder function in patients with SCI, avoiding the need for CIC. The FDA-approved implantation (Humanitarian Device Exemption H980008) of the FBBS is combined with a posterior rhizotomy to reduce reflex contraction of the bladder, improving continence. However, the posterior rhizotomy is irreversible and has unwanted effects; therefore, the current FDA-approved implantation is being studied without rhizotomy as part of a clinical trial (Investigational Device Exemption G150201) (ClinicalTrials.gov Identifier: NCT02978638). In this video, we present a case of a 66-yr-old female who presented 40-yr status post-T12 SCI, resulting in complete paraplegia and neurogenic bladder not satisfactorily controlled with CIC. We demonstrate the operative steps to complete the implantation of the device without rhizotomy in the first patient enrolled as part of the clinical trial Electrical Stimulation for Continence After SCI (NCT02978638). Appropriate IRB and patient consent were obtained.

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.

Electrical stimulation modulates Wnt signaling and regulates genes for the motor endplate and calcium binding in muscle of rats with spinal cord transection.

BACKGROUND: Spinal cord injury (SCI) results in muscle atrophy and a shift of slow oxidative to fast glycolytic fibers. Electrical stimulation (ES) at least partially restores muscle mass and fiber type distribution. The objective of this study was to was to characterize the early molecular adaptations that occur in rat soleus muscle after initiating isometric resistance exercise by ES for one hour per day for 1, 3 or 7 days when ES was begun 16 weeks after SCI. Additionally, changes in mRNA levels after ES were compared with those induced in soleus at the same time points after gastrocnemius tenotomy (GA). RESULTS: ES increased expression of Hey1 and Pitx2 suggesting increased Notch and Wnt signaling, respectively, but did not normalize RCAN1.4, a measure of calcineurin/NFAT signaling, or PGC-1ß mRNA levels. ES increased PGC-1α expression but not that of slow myofibrillar genes. Microarray analysis showed that after ES, genes coding for calcium binding proteins and nicotinic acetylcholine receptors were increased, and the expression of genes involved in blood vessel formation and morphogenesis was altered. Of the 165 genes altered by ES only 16 were also differentially expressed after GA, of which 12 were altered in the same direction by ES and GA. In contrast to ES, GA induced expression of genes related to oxidative phosphorylation. CONCLUSIONS: Notch and Wnt signaling may be involved in ES-induced increases in the mass of paralyzed muscle. Molecular adaptations of paralyzed soleus to resistance exercise are delayed or defective compared to normally innervated muscle.

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.

The central nervous system (CNS)-independent anti-bone-resorptive activity of muscle contraction and the underlying molecular and cellular signatures.

BACKGROUND: Mechanisms by which muscle regulates bone are poorly understood. RESULTS: Electrically stimulated muscle contraction reversed elevations in bone resorption and increased Wnt signaling in bone-derived cells after spinal cord transection. CONCLUSION: Muscle contraction reduced resorption of unloaded bone independently of the CNS, through mechanical effects and, potentially, nonmechanical signals (e.g. myokines). SIGNIFICANCE: The study provides new insights regarding muscle-bone interactions. Muscle and bone work as a functional unit. Cellular and molecular mechanisms underlying effects of muscle activity on bone mass are largely unknown. Spinal cord injury (SCI) causes muscle paralysis and extensive sublesional bone loss and disrupts neural connections between the central nervous system (CNS) and bone. Muscle contraction elicited by electrical stimulation (ES) of nerves partially protects against SCI-related bone loss. Thus, application of ES after SCI provides an opportunity to study the effects of muscle activity on bone and roles of the CNS in this interaction, as well as the underlying mechanisms. Using a rat model of SCI, the effects on bone of ES-induced muscle contraction were characterized. The SCI-mediated increase in serum C-terminal telopeptide of type I collagen (CTX) was completely reversed by ES. In ex vivo bone marrow cell cultures, SCI increased the number of osteoclasts and their expression of mRNA for several osteoclast differentiation markers, whereas ES significantly reduced these changes; SCI decreased osteoblast numbers, but increased expression in these cells of receptor activator of NF-κB ligand (RANKL) mRNA, whereas ES increased expression of osteoprotegerin (OPG) and the OPG/RANKL ratio. A microarray analysis revealed that ES partially reversed SCI-induced alterations in expression of genes involved in signaling through Wnt, FSH, parathyroid hormone (PTH), oxytocin, and calcineurin/nuclear factor of activated T-cells (NFAT) pathways. ES mitigated SCI-mediated increases in mRNA levels for the Wnt inhibitors DKK1, sFRP2, and sclerostin in ex vivo cultured osteoblasts. Our results demonstrate an anti-bone-resorptive activity of muscle contraction by ES that develops rapidly and is independent of the CNS. The pathways involved, particularly Wnt signaling, suggest future strategies to minimize bone loss after immobilization.

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.

Functional electrical stimulation in spinal cord injury respiratory care.

The management of chronic respiratory insufficiency and/or long-term inability to breathe independently has traditionally been via positive-pressure ventilation through a mechanical ventilator. Although life-sustaining, it is associated with limitations of function, lack of independence, decreased quality of life, sleep disturbance, and increased risk for infections. In addition, its mechanical and electronic complexity requires full understanding of the possible malfunctions by patients and caregivers. Ventilator-associated pneumonia, tracheal injury, and equipment malfunction account for common complications of prolonged ventilation, and respiratory infections are the most common cause of death in spinal cord-injured patients. The development of functional electric stimulation (FES) as an alternative to mechanical ventilation has been motivated by a goal to improve the quality of life of affected individuals. In this article, we will review the physiology, types, characteristics, risks and benefits, surgical techniques, and complications of the 2 commercially available FES strategies - phrenic nerve pacing (PNP) and diaphragm motor point pacing (DMPP).

Absence of high amplitude propagating contractions in subjects with chronic spinal cord injury.

AIM: To investigate the presence or absence of high amplitude propagating contractions (HAPC), as well as the other measures of colonic motility, in persons with spinal cord injury (SCI). METHODS: Prolonged colonic ambulatory manometric studies were performed on 14 male volunteers: 8 with SCI (mean age, 59 ± 13 years; mean duration of injury, 13 ± 4 years) and 6 healthy able-bodied controls (mean age, 57 ± 10 years). A solid-state manometry catheter was endoscopically clipped to the splenic flexure. Recording was performed for > 24 h after manometric catheter placement. RESULTS: HAPC were absent in individuals with SCI during pre-sleep, sleep, and post-sleep phases. HAPC were significantly increased after awakening in non-SCI controls (0.8 ± 0.2 HAPC/h vs 10.5 ± 2.0 HAPC/h, P < 0.005). The motility index was lower in those with SCI than in controls pre- and post-sleep (SCI vs non-SCI: Pre-sleep, 2.4 ± 0.4 vs 8.8 ± 1.9, P < 0.01; Post-sleep, 4.3 ± 0.8 vs 16.5 ± 4.5, P < 0.05). However, a sleep-induced depression of colonic motility was observed in both the SCI and non-SCI groups (Pre-sleep vs Sleep, non-SCI: 8.8 ± 1.9 vs 2.1 ± 0.9, P < 0.002; SCI: 2.4 ± 0.4 vs 0.2 ± 0.03, P < 0.001), with the motility index of those with SCI during sleep not significantly different than that of the controls. CONCLUSION: HAPC were not observed in individuals with SCI pre- or post-sleep. A sleep-induced depression in general colonic motility was evident in SCI and control subjects.

Lower-limb amputee needs assessment using multistakeholder focus-group approach.

To assess the needs of lower-limb amputees and identify differences between diabetic dysvascular amputees and traumatic amputees, we held a multistakeholder focus-group workshop whose participants included veteran lower-limb amputees, clinicians, researchers, and prosthetic device manufacturers. We conducted the initial workshop sessions as traditional focus-group meetings with homogeneous participant groups generating lists of issues relevant to the individual groups. Subsequent sessions assembled heterogeneous participant groups for a two-phase approach: Discovery and Codesign. The Discovery phase used observation and discussion to elicit specific needs. The Codesign phase focused on emergent topics and explored potential solutions. The participants identified needs associated with desired improvements to the socket system, foot and ankle components, and alignment with the residual limb. One need was a comprehensive understanding of the recovery path following amputation that could be addressed through enhanced education and communication. Another need was remote monitoring systems that could potentially improve quality of care. No dichotomy of needs between diabetic dysvascular amputees and traumatic amputees was evident among the participants of this workshop. The lively, open-ended discussions produced numerous suggestions for improving amputee quality of life that are listed to facilitate future research and development.

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.