Noninvasive spinal neuromodulation mitigates symptoms of idiopathic overactive bladder

Altres ajuts: Academy of Finland 129164Overactive bladder (OAB) affects 12 to 30% of the world's population. The accompanying urinary urgency, frequency and incontinence can have a profound effect on quality of life, leading to depression, social isolation, avoidance of sexual activity and loss of productivity. Conservative measures such as lifestyle modification and pelvic floor physical therapy are the first line of treatment for overactive bladder. Patients who fail these may go on to take medications, undergo neuromodulation or receive injection of botulinum toxin into the bladder wall. While effective, medications have side effects and suffer from poor adherence. Neuromodulation and botulinum toxin injection are also effective but are invasive and not acceptable to some patients. We have developed a novel transcutaneous spinal cord neuromodulator (SCONE™,) that delivers multifrequency electrical stimulation to the spinal cord without the need for insertion or implantation of stimulating electrodes. Previously, multifrequency transcutaneous stimulation has been demonstrated to penetrate to the spinal cord and lead to motor activation of detrusor and external urethral sphincter muscles. Here, we report on eight patients with idiopathic overactive bladder, who underwent 12 weeks of SCONE™ therapy. All patients reported statistically significant clinical improvement in multiple symptoms of overactive bladder, such as urinary urgency, frequency and urge incontinence. In addition, patients reported significant symptomatic improvements as captured by validated clinical surveys. SCONE™ therapy represents the first of its kind therapy to treat symptoms of urgency, frequency and urge urinary incontinence in patients with OAB. The study was listed on clinicaltrials.gov ()

Interleaved configurations of percutaneous epidural stimulation enhanced overground stepping in a person with chronic paraplegia

Descending motor signals are disrupted after complete spinal cord injury (SCI) resulting in loss of standing and walking. We previously restored standing and trunk control in a person with a T3 complete SCI following implantation of percutaneous spinal cord epidural stimulation (SCES). We, hereby, present a step-by-step procedure on configuring the SCES leads to initiate rhythmic lower limb activation (rhythmic-SCES) resulting in independent overground stepping in parallel bars and using a standard walker. Initially, SCES was examined in supine lying at 2 Hz before initiating stepping-like activity in parallel bars using 20 or 30 Hz; however, single lead configuration (+2, −5) resulted in lower limb adduction and crossing of limbs, impairing the initiation of overground stepping. After 6 months, interleaving the original rhythmic-SCES with an additional configuration (−12, +15) on the opposite lead, resulted in a decrease of the extensive adduction tone and allowed the participant to initiate overground stepping up to 16 consecutive steps. The current paradigm suggests that interleaving two rhythmic-SCES configurations may improve the excitability of the spinal circuitry to better interpret the residual descending supraspinal signals with the ascending proprioceptive inputs, resulting in a stepping-like motor behavior after complete SCI

The Effect of Non-invasive Spinal Cord Stimulation on Anorectal Function in Individuals With Spinal Cord Injury : A Case Series

Spinal cord injury (SCI) is a devastating condition that impacts multiple organ systems. Neurogenic bowel dysfunction (NBD) frequently occurs after a SCI leading to reduced sensation of bowel fullness and bowel movement often leading to constipation or fecal incontinence. Spinal Neuromodulation has been proven to be a successful modality to improve sensorimotor and autonomic function in patients with spinal cord injuries. The pilot data presented here represents the first demonstration of using spinal neuromodulation to activate the anorectal regions of patients with spinal cord injuries and the acute and chronic effects of stimulation. We observed that spinal stimulation induces contractions as well as changes in sensation and pressure profiles along the length of the anorectal region. In addition, we present a case report of a patient with a SCI and the beneficial effect of spinal neuromodulation on the patient's bowel program

Brain-controlled modulation of spinal circuits improves recovery from spinal cord injury.

The delivery of brain-controlled neuromodulation therapies during motor rehabilitation may augment recovery from neurological disorders. To test this hypothesis, we conceived a brain-controlled neuromodulation therapy that combines the technical and practical features necessary to be deployed daily during gait rehabilitation. Rats received a severe spinal cord contusion that led to leg paralysis. We engineered a proportional brain-spine interface whereby cortical ensemble activity constantly determines the amplitude of spinal cord stimulation protocols promoting leg flexion during swing. After minimal calibration time and without prior training, this neural bypass enables paralyzed rats to walk overground and adjust foot clearance in order to climb a staircase. Compared to continuous spinal cord stimulation, brain-controlled stimulation accelerates and enhances the long-term recovery of locomotion. These results demonstrate the relevance of brain-controlled neuromodulation therapies to augment recovery from motor disorders, establishing important proofs-of-concept that warrant clinical studies

Motor improvements enabled by spinal cord stimulation combined with physical training after spinal cord injury: Review of experimental evidence in animals and humans

Electrical spinal cord stimulation (SCS) has been gaining momentum as a potential therapy for motor paralysis in consequence of spinal cord injury (SCI). Specifically, recent studies combining SCS with activity-based training have reported unprecedented improvements in motor function in people with chronic SCI that persist even without stimulation. In this work, we first provide an overview of the critical scientific advancements that have led to the current uses of SCS in neurorehabilitation: e.g. the understanding that SCS activates dormant spinal circuits below the lesion by recruiting large-to-medium diameter sensory afferents within the posterior roots. We discuss how this led to the standardization of implant position which resulted in consistent observations by independent clinical studies that SCS in combination with physical training promotes improvements in motor performance and neurorecovery. While all reported participants were able to move previously paralyzed limbs from day 1, recovery of more complex motor functions was gradual, and the timeframe for first observations was proportional to the task complexity. Interestingly, individuals with SCI classified as AIS B and C regained motor function in paralyzed joints even without stimulation, but not individuals with motor and sensory complete SCI (AIS A). Experiments in animal models of SCI investigating the potential mechanisms underpinning this neurorecovery suggest a synaptic reorganization of cortico-reticulo-spinal circuits that correlate with improvements in voluntary motor control. Future experiments in humans and animal models of paralysis will be critical to understand the potential and limits for functional improvements in people with different types, levels, timeframes, and severities of SCI

Enhancing Nervous System Recovery through Neurobiologics, Neural Interface Training, and Neurorehabilitation.

After an initial period of recovery, human neurological injury has long been thought to be static. In order to improve quality of life for those suffering from stroke, spinal cord injury, or traumatic brain injury, researchers have been working to restore the nervous system and reduce neurological deficits through a number of mechanisms. For example, neurobiologists have been identifying and manipulating components of the intra- and extracellular milieu to alter the regenerative potential of neurons, neuro-engineers have been producing brain-machine and neural interfaces that circumvent lesions to restore functionality, and neurorehabilitation experts have been developing new ways to revitalize the nervous system even in chronic disease. While each of these areas holds promise, their individual paths to clinical relevance remain difficult. Nonetheless, these methods are now able to synergistically enhance recovery of native motor function to levels which were previously believed to be impossible. Furthermore, such recovery can even persist after training, and for the first time there is evidence of functional axonal regrowth and rewiring in the central nervous system of animal models. To attain this type of regeneration, rehabilitation paradigms that pair cortically-based intent with activation of affected circuits and positive neurofeedback appear to be required-a phenomenon which raises new and far reaching questions about the underlying relationship between conscious action and neural repair. For this reason, we argue that multi-modal therapy will be necessary to facilitate a truly robust recovery, and that the success of investigational microscopic techniques may depend on their integration into macroscopic frameworks that include task-based neurorehabilitation. We further identify critical components of future neural repair strategies and explore the most updated knowledge, progress, and challenges in the fields of cellular neuronal repair, neural interfacing, and neurorehabilitation, all with the goal of better understanding neurological injury and how to improve recovery

Principles of Rehabilitation Strategies in Spinal Cord Injury

Spinal cord injury (SCI) is a debilitating condition that affects millions of people worldwide and results in a remarkable health economic burden imposed on patients and the healthcare system annually. The most common causes of SCI are the trauma caused by falls, traffic accidents, or violence. The course of SCI is associated with several complications that severely impair the patient’s quality of life, including sensory and motor dysfunction, pain, neurogenic bladder and bowel, autonomic dysreflexia, cardiovascular and pulmonary dysfunction, spasticity, urinary tract infection, and sexual dysfunction. Despite great strides that have been made in the field of regenerative medicine and neural repair, the treatment of SCI still mostly revolves around rehabilitative strategies to improve patients’ quality of life and function. Rehabilitation following the SCI is a multidisciplinary process that requires the involvement of multiple disciplines. Moreover, recent advances in the field of neurorehabilitation following SCI, are changing the face of this field. Therefore, we decided to review various aspects of rehabilitation following the SCI, including the goals and different modalities whereby we could achieve them

Spinal Cord Injury and Transcutaneous Spinal Cord Stimulation

Recent research of epidural and transcutaneous electrical spinal cord stimulation has demonstrated unprecedented improvements in motor function thought to be irreversibly lost due to chronic, severe spinal cord injury. Studies in parallel assess these methods for spasticity management as an alternative to medications that are often accompanied by deleterious side effects. As a noninvasive intervention, transcutaneous spinal cord stimulation holds the great potential to find its way into wide clinical application. Its firm establishment and lasting acceptance as clinical practice in spinal cord injury will not only hinge on the demonstration of safety and efficacy, but also on the delineation of a conceptual framework of the underlying physiological mechanisms. This will also require advancing our understanding of immediate and temporary effects of transcutaneous spinal cord on neuronal circuits in the intact and injured spinal cord. The purpose of this collection of papers is to bring together peers in the field to share—and eventually fuse—their pertinent research into current neurorehabilitation practice by providing a clinical perspective and novel insights into the underlying mechanisms

Spinal Cord Stimulation for Spinal Cord Injury

Spinal cord injury is a medically complex and life-disrupting condition, associated with very high mortality rates (early death rates after admission range from 4 to 20%). In addition, it’s complicated subsequent severe disability due to the development of early or late complications. Today, in high-income countries, SCI can be viewed less as the end of a worthwhile or productive life and more as a personal and social challenge that can be successfully overcome. SCI can be divided into two types of injury on the basis of severity: complete and incomplete injury. Damage to the spinal cord may be traumatic (falls, road traffic injuries, occupational and sports injuries, violence) or non-traumatic (infectious disease, tumor, musculoskeletal disease, congenital problems such as spina bifid)